KR20100125079A - Peptide mixture extracted from human placenta, and preparation method and use thereof - Google Patents

Abstract

PURPOSE: A placenta-derived peptide mixture is provided to induce bone differentiation and to treat bone diseases. CONSTITUTION: A placenta-derived peptide is prepared by hydrolyzing placenta in pH 2-3 acid solution at 95-105°C. The acid is acetic acid, trifluoroacetic acid or formic acid. The placenta is from human or pig. The peptide has a sequence selected from sequence numbers 1-129. A composition for inducing differentiation of stem cells to bone contains the peptide mixture as an active ingredient. A composition for preventing or treating bone diseases contains the peptide mixture as an active ingredient.

Description

Peptide mixture extracted from human placenta, and preparation method and use

A placental-derived peptide mixture extracted from the placenta, a method of preparing a peptide mixture from the placenta, comprising hydrolyzing the placenta with a weak acid solution, and a use in inducing bone differentiation of the peptide mixture is provided.

Placenta is also called Jahager in the herbal medicine, and its constituents contain dozens of amino acids, peptides, vitamins, polysaccharides, nucleic acids, minerals, and enzymes in addition to essential amino acids. In addition, it contains various growth factors and cytokines, and is known to be useful for fatigue recovery and immune enhancement.

In addition, the placenta has the effect of inhibiting the activity of the enzyme tyrosinase, which catalyzes the production of melanin granules from the amino acid tyrosine, thereby inhibiting the production of melanin pigments and promoting the release of cells containing melanin pigments. It is effective in prevention and improvement, and eventually shows whitening as well as preventing pigmentation.

In addition, the tissue metabolism promoting action of the placenta increases sebum secretion function to normalize the secretion of sebum as a result of reducing or removing the wrinkles. When the dermal tissue loses its elasticity, deep wrinkles and sagging skin occur. In the dermal tissue, fibroblasts produce collagen and elastin that binds the collagen, and hyaluronic acid that fills it. Therefore, the decline of fibroblasts causes deep wrinkles. The placenta contains fibroblast growth factor (FGF), which promotes the proliferation and regeneration of fibroblasts and activates the amount of collagen, elastin and hyaluronic acid. It increases the elasticity and elasticity of the skin to improve deep wrinkles and sagging skin.

In view of the effect of promoting the growth and proliferation of the placenta, there have been attempts to extract the active ingredient from the placenta of humans or animals and use it for cosmetics or medicine. As a conventional placenta extraction method, hydrolysis using strong acid (usually 3N hydrochloric acid) or strong alkali has been performed, but in this method, various amino acids, growth promoters, cytokines, There is a problem that the bioactive substances such as hyaluronic acid, growth factors are inactivated or extinguished. In addition to the acid treatment method, a method using a hydrolase has been used, but it has been pointed out as a disadvantage in that the hydrolase is included as an impurity in the placenta extract and in the part of the expensive production process and the reproducibility of the reaction. Therefore, it is necessary to develop a method of improving such a problem and ensuring a simple and low-cost repeatability.

In addition, physiological and chemical verification of the effect of placenta extract was not scientifically conducted through appropriate procedures. Therefore, it is necessary to verify the effects of hydrolyzate in scientific systems.

The present inventors have completed the present invention by confirming that the placenta extract containing a new active ingredient can be obtained by hydrolyzing the placenta in a peptide state under specific conditions.

Thus, one example of the present invention provides a placental peptide mixture obtained by hydrolysis of the placenta at 95 to 105 ℃ with an acetic acid solution of pH 2-3.

Another example of the present invention provides a composition for inducing differentiation into osteoblasts containing the placental peptide mixture as an active ingredient.

Another example of the present invention provides a composition for preventing and / or ameliorating and / or treating bone disease, which contains the placental peptide mixture as an active ingredient.

Another example of the present invention provides a method for producing a placental peptide mixture comprising the step of hydrolysis by adding an acetic acid solution of pH 2-3 to the placenta.

Another example of the present invention provides a method for inducing bone differentiation of stem cells comprising culturing the mesenchymal stem cells isolated from the bone marrow with the peptide mixture.

The present invention relates to a peptide mixture obtained by hydrolysis of the placenta with an acid solution of pH 2-3 at 95-105 ° C.

Previously, placenta was hydrolyzed at high temperature for a long time using a strong acid such as hydrochloric acid or strong alkali and / or pepsin to obtain placenta extract. In this case, the protein present in the placenta is completely decomposed to exist as an amino acid. . As such, the protein is completely decomposed into an amino acid state and undergoes a high temperature treatment, thereby deactivating or disappearing bioactive substances such as amino acids, growth promoters, cytokines, and hyaluronic acid.

However, as in the present invention, when the placenta is hydrolyzed to at least one selected from the group consisting of weak acids of pH 2-3, such as acetic acid, trifluoroacetic acid (TFA), and formic acid, in the temperature range of 95 to 105 ℃ The protein contained in the placenta is not completely degraded to the amino acid state but to the peptide state of about 7 to 40 amino acids in length. The amino acids present in the hydrolyzate obtained by decomposing the placenta with strong acids or strong alkalis and / or hydrolases, as in the conventional method, cannot function as functional units, but the peptides in the peptide mixture obtained according to the present invention are at least capable of functioning. It has an advantage in that it acts as a new effective ingredient capable of exhibiting a predetermined function by having a length of.

The placenta applicable in the present invention is not particularly limited, and may be, for example, placenta or placenta. When the pH is too low during hydrolysis, the hydrolytic selectivity (only aspartic acid sites are degraded) is degraded, so that the protein is completely decomposed into amino acids similar to the case of using a strong acid, and the high pH lowers the efficiency of the hydrolysis reaction. In order to obtain a proper hydrolysis effect without being completely decomposed, it is important to proceed with hydrolysis by adjusting the pH to a range of 2 to 3 using a weak acid. If the pH is within the above range, there is no significant limitation on the kind of weak acid that can be used. For example, one or more selected from the group consisting of acetic acid, trifluoroacetic acid (TFA), formic acid, and the like can be used. In addition, in order to effectively decompose the protein into peptides, the hydrolysis temperature is preferably about 95 ° C. or more, and about 105 ° C. or less in order to prevent denaturation by heat of the obtained peptide. Therefore, the hydrolysis temperature of the placenta is preferably carried out at 95 to 105 ℃. The hydrolysis time may be 1 to 4 hours, but not limited thereto, in order to obtain sufficient and adequate hydrolysis results.

Under such conditions, only the aspartic acid site is selectively hydrolyzed to obtain various peptide components. As described above, when the acidity (pH) is lowered, hydrolysis of the aspartic acid site of hydrolysis is poor, and hydrolysis is not performed in the form of peptides, but in amino acid form, as in the case of strong acid. .

As such, as a result of analyzing the components contained in the hydrolyzate obtained by hydrolysis of the placenta at 95 to 105 ° C. with a weak acid of pH 2-3, various peptides of about 7-40 amino acids, preferably 7-30 amino acids in length Appeared to be present (see Examples). These peptides are thought to act as new active ingredients, each having its own function by having an amino acid length sufficient to function.

The peptides analyzed are 7-40, preferably 7-30 amino acids long peptides derived from the following proteins, ie 7-40, preferably 7-30 amino acids in sequence in the amino acid sequence of the following proteins. Peptides with:

Hemoglobin subunit beta (e.g., Accession No. P6887), hemoglobin subunit gamma-1 (e.g., Accession No. P69891), H3L (H3-Histone H3-like, e.g. Accession No. Q6NXT2), chorionic somatomammotropin hormone (e.g., Accession No. P01243), vitronectin (e.g., Accession No. P04004), Fibronectin (e.g., Accession No. P02751) , Annexin A5 (such as Accession No. P08758), annexin A2 (such as Accession No. P07355), ACTB (Actin, cytoplasmic 1 such as Accession No. P60709), immunoglobulin gamma -3 chain C region (eg Accession No. P01860), hemoglobin subunit alpha (eg Accession No. P69905), mitochondrial malate dehydrogenase (Malate dehydrogenase, mitochondrial, For example, Accession No. P40926), S10A B (Protein S100-A11, such as Accession No. P31949), Annexin A1 (Annexin A1, such as Accession No. P04083), Annexin A3 (Annexin A3, such as Accession No. P12429), Mitochondrial 10 kD heat shock protein ( 10 kDa heat shock protein, mitochondrial such as Accession No. P61604, serum albumin such as Accession No. P02768), ACTA (Actin, aortic smooth muscle, such as Accession No. P62736), ERH (Enhancer of rudimentary homolog, such as Accession No. P84090), guanine nucleotide binding protein G (I) / G (S) / G (O) Guanine nucleotide-binding protein G (I) / G (S) / G (O) subunit gamma-12, such as Accession No. Q9UBI6), protein-glutamine gamma-glutamyltransferase 2 (Protein-glutamine gamma-glutamyltransferase 2, such as Accession No. P21980), Ras-related C3 botulinum toxin substrate 2 (such as Accession No. P63000), mitochondrial ATP synthase sub Unit alpha (ATP synthase subunit alpha, mitochondrial such as Accession No. P25705), prohibitin such as Accession No. P35232, amine oxidase [flavin-containing] A (Amine oxidase [flavin-containing] A such as Accession No. P21397), TINAL (Tubulointerstitial nephritis antigen-like such as Acces sion No. Q9GZM7), apolipoprotein A-1 (Apolipoprotein AI, such as Accession No. P02647), mitochondrial 60 kD heat shock protein (60 kDa heat shock protein, mitochondrial such as Accession No. P10809), superoxide dismutase [Cu-Zn] (Superoxide dismutase [Cu-Zn], such as Accession No. P00441), NADH-cytochrome b5 reductase 1 (e.g., Accession No. Q9UHQ9), neuron-specific calcium-binding protein hippocalcin, e.g., Accession No. P84074), S10A6 (Protein S100-A6, such as Accession No. P06703), mitochondrial ATP synthase subunit delta (mitochondrial, such as Accession No. P30049), Carbonic anhydrase 1, For example, Accession No. P00915), Clustererin (eg, Accession No. P10909), Myosin regulatory light chain MRLC2 (eg, Accession No. O14950), Annexin A6 (eg, Accession No. P08133), transmembrane glycoprotein NMB such as Accession No. Q14956, Collagen alpha-3 (VI) chain such as Accession No. P12111), Galectin-1 (eg, Accession No. P09382), fibrino Fibrinogen beta chain (e.g., Accession No. P02675), alpha-2-HS-glycoprotein (e.g., Accession No. P02765), cell division control protein 42 (Cell division control protein 42 homolog such as Accession No. P60953), serotransferrin such as Accession No. P02787), Annex A4 (eg, Accession No. P09525), S10AA (Protein S100-A10, such as Accession No. P60903), Synaptic glycoprotein SC2 (eg, Accession No. Q9NZ01), Guanine nucleotide-binding protein G (I) / G (S) / G (O) subunit gamma-5, For example, Accession No. P63218), Tallin-1 (e.g., Accession No. Q9Y490), Tripeptidyl Peptidase 1 (e.g., Accession No. O14773), Mitochondrial 3-ketoacyl- CoA thiolase (3-ketoacyl-CoA thiolase, mitochondrial, such as Accession No. P42765), mitochondrial glutamate dehydrogenase 1 (Glutamate dehydrogenase 1, mitochondrial, such as Accession No. P00367), nidogen-2 (Nidogen-2, Eg, Accession No. Q14112), alpha-2-HS-glycoprotein (eg, Accession No. P02765), peptidyl-prolyl cis-trans isomere Izu B (Peptidyl-prolyl cis-trans isomerase B such as Accession No. P23284), mitochondrial ATP synthase subunit beta (mitochondrial such as Accession No. P06576), NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2, such as Accession No. 1). O43678), Clathrin heavy chain 1 (e.g., Accession No. Q00610), Basement membrane-specific heparan sulfate proteoglycan core protein (e.g., Accession No. P98160) , K0146 (Uncharacterized protein KIAA0146, such as Accession No. Q14159), Apolipoprotein (a) (Apolipoprotein (a), such as Accession No. P08519), and mitochondrial thioredoxin (Thioredoxin, mitochondrial, such as Accession No. Q99757).

Hereinafter, the peptide derived from the protein will be described in more detail.

In the case of Hemoglobin subunit beta (Accession No. P6887), 7-40 amino acids consecutive from 71st amino acid to 110th amino acid, preferably 7-30 amino acids consecutive from 71th to 100th amino acid It may be one or more selected from the group consisting of peptides having a amino acid sequence of SEQ ID NO: 1 to 8, for example.

For hemoglobin subunit gamma-1 (e.g., Accession No. P69891), peptides having 7-30 amino acids contiguous among 21st to 50th or 76th to 105th, such as It may be one or more selected from the group consisting of peptides having an amino acid sequence of SEQ ID NO: 9 to 15.

In the case of H3L (H3-Histone H3-like, eg, Accession No. Q6NXT2), a peptide having 7-30 amino acids in sequence from the 101st to the 130th, such as a peptide having the amino acid sequence of SEQ ID NOs: 16 and 17 It may be one or more selected from the group consisting of.

In the case of chorionic somatomammotropin hormone (e.g., Accession No. P01243), a peptide having 7-30 amino acids consecutive from the 171th to the 200th, such as the amino acid sequence of SEQ ID NOs: 18 to 20 It may be one or more selected from the group consisting of a peptide having.

In the case of Vitronectin (Vitronectin, Accession No. P04004), it may be at least one selected from the group consisting of peptides having 7-30 amino acids consecutive from 449th to 478th, for example, the amino acid sequence of SEQ ID NO: 21 It may be a peptide having.

Fibronectin (e.g., Accession No. P02751), a peptide having 7-30 amino acids consecutively from 1506 to 1535, or 2121 to 2150, such as a peptide having the amino acid sequence of SEQ ID NOs: 22 to 24 It may be one or more selected from the group consisting of.

In the case of Annexin A5 (e.g., Accession No. P08758), a peptide having 7-30 amino acids contiguous among 66th to 95th or 291th to 320th, for example, amino acids of SEQ ID NOs: 25 to 28 It may be one or more selected from the group consisting of peptides having a sequence.

In case of Annexin A2 (e.g., Accession No. P07355), it has 7-40 amino acids consecutive from 1st to 40th and / or 7-30 amino acids consecutive from 310th to 339th. It may be at least one selected from the group consisting of peptides such as peptides having the amino acid sequence of SEQ ID NOs: 29 to 34.

In the case of ACTB (Actin, cytoplasmic 1, such as Accession No. P60709), a peptide having 7-30 amino acids in sequence from 206 to 235 or 346 to 375, such as amino acids of SEQ ID NOs: 35 to 37 It may be one or more selected from the group consisting of peptides having a sequence.

In the case of an immunoglobulin gamma-3 chain C region (eg, Ig gamma-3 chain C region, eg, Accession No. P01860), a peptide having 7-30 amino acids in sequence from the 276 th to the 305 th such as SEQ ID NO: 38 It may be one or more selected from the group consisting of peptides having an amino acid sequence of from 40 to 40.

In the case of hemoglobin subunit alpha (eg, Accession No. P69905), a peptide having 7-40 amino acids in sequence among the 91st to 142th, such as a peptide having the amino acid sequence of SEQ ID NOs: 41 to 43 It may be one or more selected from the group consisting of.

For mitochondrial malate dehydrogenase (Malate dehydrogenase, such as Accession No. P40926), peptides having 7-40 amino acids consecutive from 21st to 60th or 181th to 220th, such as SEQ ID NOs: 44 to It may be one or more selected from the group consisting of peptides having an amino acid sequence of 47.

In the case of S10AB (Protein S100-A11, such as Accession No. P31949), a group having peptides having 7 to 40 amino acids consecutively from 1st to 60th, for example, a group having peptides having an amino acid sequence of SEQ ID NOs: 48 to 50 It may be one or more selected from.

In case of Annexin A1 (e.g., Accession No. P04083), a group consisting of peptides having 7-30 amino acids in sequence among the 91st to 120th, such as peptides having the amino acid sequences of SEQ ID NOs: 51 and 52 It may be one or more selected from.

Annexin A3 (eg, Accession No. P12429) may be one or more selected from the group consisting of peptides having 7-30 amino acid sequences consecutive from 194 th to 323 th, for example, SEQ ID NO: It may be a peptide having an amino acid sequence of 53.

For mitochondrial 10 kD heat shock proteins (mitochondrial, such as Accession No. P61604), peptides having 7-30 amino acids consecutive from 1st to 30th, such as amino acid sequences of SEQ ID NOs: 54 and 55 It may be one or more selected from the group consisting of a peptide having.

In the case of serum albumin (e.g., Accession No. P02768), peptides having sequences of 7-30 amino acids in sequence from 191 to 220, 326 to 355, or 381 to 410, such as sequences It may be one or more selected from the group consisting of peptides having amino acid sequences of Nos. 56 to 62.

In the case of ACTA (Actin, aortic smooth muscle, eg, Accession No. P62736), peptides having 7-30 amino acids in sequence from 206th to 235th or 348th to 377th, such as SEQ ID NOs: 63-65 It may be one or more selected from the group consisting of peptides having an amino acid sequence.

In the case of the Enhancer of rudimentary homolog (e.g., Accession No. P84090), a group consisting of peptides having 7-30 amino acids consecutive from the 61st to the 90th, such as a peptide having the amino acid sequence of SEQ ID NOs: 66 to 68 It may be one or more selected from.

Guanine nucleotide-binding protein G (I) / G (S) / G (O) subunit gamma-12, such as, for example, Guanine nucleotide binding protein G (I) / G (S) / G (O) subunit gamma-12 Accession No. Q9UBI6) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 41st to 70th, for example, may be a peptide having the amino acid sequence of SEQ ID NO: 69. .

For Protein-glutamine gamma-glutamyltransferase 2 (e.g., Accession No. P21980), 7-30 amino acids consecutive from 1st to 30th or from 186th to 215th It may be one or more selected from the group consisting of a peptide having, for example, a peptide having an amino acid sequence of SEQ ID NO: 70 to 73.

For Ras-related C3 botulinum toxin substrate 1 (e.g., Accession No. P63000), in the group consisting of peptides having 7-30 amino acids consecutive from 1st to 30th It may be one or more selected, for example, may be a peptide having a sequence of SEQ ID NO: 74.

In the case of mitochondrial ATP synthase subunit alpha (mitochondrial, e.g., Accession No. P25705), at least one member selected from the group consisting of peptides having 7-30 amino acids consecutive from 524 th to 553 th For example, it may be a peptide having an amino acid sequence of SEQ ID NO: 75.

In the case of Prohibitin (e.g., Accession No. P35232), peptides having 7-30 amino acid sequences consecutive among the 41st to 70th or 111th to 140th, for example, SEQ ID NOs: 76 to 78 It may be one or more selected from the group consisting of peptides having an amino acid sequence.

Amine oxidase [flavin-containing] A (e.g., Accession No. P21397), a group consisting of peptides having 7-30 amino acids in sequence from the 336th to the 365th It may be one or more selected from, for example, may be a peptide having an amino acid sequence of SEQ ID NO: 79.

In the case of TINAL (Tubulointerstitial nephritis antigen-like, eg, Accession No. Q9GZM7), a peptide having 7-30 amino acids in sequence from the 236th to the 270th, for example, a peptide having the amino acid sequence of SEQ ID NOs: 80 to 83 It may be one or more selected from the group consisting of.

Apolipoprotein A-1 (for example, Accession No. P02647) is selected from the group consisting of peptides having 7-40, preferably 7-35, amino acids consecutive from the 228th to the 367th. It may be one or more, for example, may be a peptide having the amino acid sequence of SEQ ID NO: 84.

In the case of a mitochondrial 60 kD heat shock protein (mitochondrial, for example, Accession No. P10809), may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 541 th to 560 th And for example, a peptide having the amino acid sequence of SEQ ID NO: 85.

In the case of Superoxide dismutase [Cu-Zn], such as Accession No. P00441, peptides having 7-30 amino acids in sequence from 1st to 30th, eg sequences It may be one or more selected from the group consisting of peptides having the amino acid sequence of the number 86 and 87.

For NADH-cytochrome b5 reductase 1 (e.g., Accession No. Q9UHQ9), 1 selected from the group consisting of peptides having 7-30 amino acids consecutive from the 201st to the 230th It may be a species or more, for example, may be a peptide having the amino acid sequence of SEQ ID NO: 88.

In the case of neuron-specific calcium-binding protein hippocalcin (e.g., Accession No. P84074), it is selected from the group consisting of peptides having 7-30 amino acids in sequence from 164th to 193th. It may be one or more, for example, may be a peptide having the amino acid sequence of SEQ ID NO: 89.

S10A6 (Protein S100-A6, such as Accession No. P06703) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 1st to 30th, for example SEQ ID NO: It may be a peptide having an amino acid sequence of 90.

In the case of mitochondrial ATP synthase subunit delta (mitochondrial, e.g., Accession No. P30049), one or more selected from the group consisting of peptides having 7-40 amino acids consecutive from 56th to 95th For example, it may be a peptide having an amino acid sequence of SEQ ID NO: 91.

Carbonic anhydrase 1 (eg, Accession No. P00915) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 136th to 165th, for example, a sequence It may be a peptide having an amino acid sequence of the number 92.

In the case of Clustererin (eg, Accession No. P10909), it may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 391 th to 420 th, for example SEQ ID NO: 93 It may be a peptide having an amino acid sequence of.

In the case of myosin regulatory light chain MRLC2 (e.g., Accession No. O14950), a peptide having 7-30 amino acids in sequence from the 91st to 120th, for example, amino acid sequences of SEQ ID NOs: 94 and 96 It may be one or more selected from the group consisting of a peptide having.

In case of Annexin A6 (eg, Accession No. P08133), it may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 644 th to 673 th, for example, SEQ ID NO: It may be a peptide having an amino acid sequence of 97.

In the case of transmembrane glycoprotein NMB (eg, Accession No. Q14956), the transmembrane glycoprotein NMB may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 251 th to 280 th, for example It may be a peptide having the amino acid sequence of SEQ ID NO: 98.

In the case of the Collagen alpha-3 (VI) chain (e.g., Accession No. P12111), 7-30 amino acids are contiguous among the 976th to 1105th, or the 1646th to 1675th. It may be one or more selected from the group consisting of peptides having a amino acid sequence of SEQ ID NO: 99 and 100, for example.

For galectin-1 (e.g., Accession No. P09382), a peptide having 7-30 amino acids consecutive from 106th to 135th, for example, a peptide having the amino acid sequence of SEQ ID NOs: 101 and 102 It may be one or more selected from the group consisting of.

In the case of Fibrinogen beta chains (e.g., Accession No. P02675), 7-30 amino acids are contiguous in the 251st to 280th, or 306th to 335th, and in the 291th to 330rd It may be one or more selected from the group consisting of peptides having an amino acid sequence of 7-40 amino acids, for example SEQ ID NO: 103 and 106.

In the case of alpha-2-HS-glycoprotein (eg, Accession No. P02765), 1 selected from the group consisting of peptides having 7-30 amino acids in sequence from the 338th to the 367th It may be a species or more, for example, may be a peptide having the amino acid sequence of SEQ ID NO: 107.

Cell division control protein 42 homolog (eg, Accession No. P60953) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 1st to 30th And for example, a peptide having the amino acid sequence of SEQ ID NO: 108.

In the case of Serotransferrin (e.g., Accession No. P02787), peptides having 7-30 amino acids in sequence from the 101st to 130th, or the 491th to 520th, for example, amino acids of SEQ ID NOs: 109 and 110 It may be one or more selected from the group consisting of peptides having a sequence.

In case of Annex A4 (eg, Accession No. P09525), it may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 290 th to 319 th, for example, SEQ ID NO: It may be a peptide having an amino acid sequence of 111.

S10AA (Protein S100-A10, for example, Accession No. P60903) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 1st to 30th, for example, SEQ ID NO: It may be a peptide having an amino acid sequence of 112.

Synaptic glycoprotein SC2 (eg, Accession No. Q9NZ01) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 279 th to 308 th, for example, It may be a peptide having the amino acid sequence of SEQ ID NO: 113.

Guanine nucleotide-binding protein G (I) / G (S) / G (O) subunit gamma-5, For example, Accession No. P63218) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 36th to 65th, for example, a peptide having an amino acid sequence of SEQ ID NO. Can be.

In the case of Talin-1 (eg, Accession No. Q9Y490), it may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 661 th to 700 th, for example, It may be a peptide having the amino acid sequence of SEQ ID NO: 115.

In the case of tripeptidyl peptidase 1 (eg, Accession No. O14773), the peptide may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 534 th to 563 th For example, it may be a peptide having the amino acid sequence of SEQ ID NO: 116.

For mitochondrial 3-ketoacyl-CoA thiolase (3-ketoacyl-CoA thiolase, mitochondrial, such as Accession No. P42765), in the group consisting of peptides having 7-30 amino acids consecutive from 1st to 30th It may be one or more selected, for example, may be a peptide having the amino acid sequence of SEQ ID NO: 117.

For mitochondrial glutamate dehydrogenase 1 (mitochondrial, such as Accession No. P00367), may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 529 to 558th For example, it may be a peptide having the amino acid sequence of SEQ ID NO: 118.

Nidogen-2 (eg, Accession No. Q14112) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 1271 th to 1300 th, for example, It may be one or more selected from the group consisting of peptides having amino acid sequences of SEQ ID NOs: 119 and 120.

In the case of alpha-2-HS-glycoprotein (eg, Accession No. P02765), 1 selected from the group consisting of peptides having 7-30 amino acids in sequence from 116th to 145th It may be a species or more, for example, may be a peptide having the amino acid sequence of SEQ ID NO: 121.

In the case of Peptidyl-prolyl cis-trans isomerase B (e.g., Accession No. P23284), a peptide having 7-30 amino acids in sequence from the 51st to the 80th It may be one or more selected from the group consisting of, for example, may be a peptide having the amino acid sequence of SEQ ID NO: 122.

In the case of mitochondrial ATP synthase subunit beta (mitochondrial, such as Accession No. P06576), at least one member selected from the group consisting of peptides having 7-30 amino acids consecutive from 366 th to 406 th For example, it may be a peptide having an amino acid sequence of SEQ ID NO: 123.

For NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 (e.g., Accession No. O43678), 7-30 amino acids consecutive from the 41st to the 70th It may be one or more selected from the group consisting of a peptide having, for example, may be a peptide having the amino acid sequence of SEQ ID NO: 124.

Clathrin heavy chain 1 (eg, Accession No. Q00610) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 1466 th to 1495 th, for example It may be a peptide having the amino acid sequence of SEQ ID NO: 125.

Basement membrane-specific heparan sulfate proteoglycan core protein (e.g., Accession No. P98160) is a peptide having 7-30 amino acids in sequence from 1206 to 1235. It may be one or more selected from the group consisting of, for example, may be a peptide having the amino acid sequence of SEQ ID NO: 126.

K0146 (Uncharacterized protein KIAA0146, for example, Accession No. Q14159) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from the 101-130th, for example SEQ ID NO: 127 It may be a peptide having an amino acid sequence of.

Apolipoprotein (a) (eg, Accession No. P08519) may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from 4491 th to 4520 th For example, it may be a peptide having an amino acid sequence of SEQ ID NO: 128.

For mitochondrial thioredoxin (Thioredoxin, mitochondrial, such as Accession No. Q99757), may be one or more selected from the group consisting of peptides having 7-30 amino acids consecutive from the 137th to 166th, for example, It may be a peptide having the amino acid sequence of SEQ ID NO: 129.

Thus, in an embodiment of the present invention, the peptide of 7-40 amino acids in length derived from the proteins may be one or more selected from the group consisting of peptides having an amino acid sequence of SEQ ID NO: 1 to 129.

As described above, the peptide mixture obtained according to the present invention is obtained by specifically hydrolyzing only aspartic acid, wherein the hydrolysis occurs randomly at the N- and C-terminals of aspartic acid. -40 or 7-30 amino acids can range from aspartic acid present in the interval or the amino acid located immediately after to aspartic acid existing within or within the 40th amino acid or the amino acid located immediately before.

Examples of peptide types present in placental peptide mixtures according to the present invention and the proteins from which they are derived are summarized in Table 1 below.

TABLE 1

Protein (UniProtKB) Accession No. Peptide HBB_HUMAN Hemoglobin subunit beta GN = HBB PE = 1 SV = 2_2_147 P68871 D.NLKGTFATLSELHC.D (SEQ ID NO: 1)
D.NLKGTFATLSELHCD.K (SEQ ID NO: 2)
D.NLKGTFATLSELHCDKLHV.D (SEQ ID NO: 3)
D.GLAHLDNLKGTFATLSELHC.D (SEQ ID NO: 4)
D.NLKGTFATLSELHCDKLHVD.P (SEQ ID NO: 5)
D.GLAHLDNLKGTFATLSELHCD.K (SEQ ID NO: 6)
D.GLAHLDNLKGTFATLSELHCDKLHV.D (SEQ ID NO: 7)
D.GLAHLDNLKGTFATLSELHCDKLHVD.P (SEQ ID NO: 8) HBG1_HUMAN Hemoglobin subunit gamma-1 GN = HBG1 PE = 1 SV = 2_2_147 P69891 D.LKGTFAQLSELHC.D (SEQ ID NO: 9)
D.DLKGTFAQLSELHC.D (SEQ ID NO: 10)
D.LKGTFAQLSELHCD.K (SEQ ID NO: 11)
D.LKGTFAQLSELHCDKLHV.D (SEQ ID NO: 12)
D.LKGTFAQLSELHCDKLHVD.P (SEQ ID NO: 13)
D.AGGETLGRLLVVYPWTQRFF.D (SEQ ID NO: 14)
D.AGGETLGRLLVVYPWTQRFFD.S (SEQ ID NO: 15) H3L_HUMAN Histone H3-like PE = 2 SV = 3_2_135 Q6NXT2 D.TNLCAIHAKRVTIMPK.D (SEQ ID NO: 16)
D.TNLCAIHAKRVTIMPKD.I (SEQ ID NO: 17) CSH_HUMAN Chorionic somatomammotropin hormone GN = CSH1 PE = 1 SV = 2_27_217 P01243 D.ALLKNYGLLYCFRK.D (SEQ ID NO: 18)
D.ALLKNYGLLYCFRKD.M (SEQ ID NO: 19)
D.ALLKNYGLLYCFRKDM.D (SEQ ID NO: 20) VTNC_HUMAN Vitronectin GN = VTN PE = 1 SV = 1_20_478 P04004 D.PPYPRSIAQYWLGCPAPGHL.- (SEQ ID NO: 21) FINC_HUMAN Fibronectin GN = FN1 PE = 1 SV = 3_32_2386 P02751 D.YTITVYAVTGRG.D (SEQ ID NO: 22)
D.TSEYIISCHPVGT.D (SEQ ID NO: 23)
D.TSEYIISCHPVGTD.E (SEQ ID NO: 24) ANXA5_HUMAN Annexin A5 GN = ANXA5 PE = 1 SV = 2_2_320 P08758 D.YKKALLLLCGE.D (SEQ ID NO: 25)
D.YKKALLLLCGED.D (SEQ ID NO: 26)
D.TSGDYKKALLLLCGE.D (SEQ ID NO: 27)
D.LKSELTGKFEKLIVALMKPSRLY.D (SEQ ID NO 28) ANXA2_HUMAN Annexin A2 GN = ANXA2 PE = 1 SV = 2_2_339 P07355 D.YQKALLYLCGG.D (SEQ ID NO: 29)
D.YQKALLYLCGGD.D (SEQ ID NO: 30)
-.STVHEILCKLSLEG.D (SEQ ID NO: 31)
D.TKGDYQKALLYLCGG.D (SEQ ID NO: 32)
-.STVHEILCKLSLEGD.H (SEQ ID NO: 33)
-.STVHEILCKLSLEGDHSTPPSAYGSVKAYTNF.D (SEQ ID NO: 34) ACTB_HUMAN Actin, cytoplasmic 1 GN = ACTB PE = 1 SV = 1_1_375 P60709 D.IKEKLCYVAL.D (SEQ ID NO: 35)
D.IKEKLCYVALD.F (SEQ ID NO: 36)
D.ESGPSIVHRKCF.- (SEQ ID NO: 37) IGHG3_HUMAN Ig gamma-3 chain C region GN = IGHG3 PE = 1 SV = 2_1_377 P01860 D.TLMISRTPEVTCVVV.D (SEQ ID NO: 38)
D.TLMISRTPEVTCVVVD.V (SEQ ID NO: 39)
D.TLMISRTPEVTCVVVDVSHE.D (SEQ ID NO: 40) HBA_HUMAN Hemoglobin subunit alpha GN = HBA1 PE = 1 SV = 2_2_142 P69905 D.KFLASVSTVLTSKYR.- (SEQ ID NO: 41)
D.PVNFKLLSHCLLVTLAAHLPAEFTPAVHASL.D (SEQ ID NO: 42)
D.PVNFKLLSHCLLVTLAAHLPAEFTPAVHASLD.K (SEQ ID NO: 43)  MDHM_HUMAN Malate dehydrogenase, mitochondrial GN = MDH2 PE = 1 SV = 3_25_338 P40926 D.PARVNVPVIGGHAGKTIIPLISQCTPKV.D (SEQ ID NO: 44)
D.PARVNVPVIGGHAGKTIIPLISQCTPKVD.F (SEQ ID NO: 45)
-.AKVAVLGASGGIGQPLSLLLKNSPLVSRLTLY.D (SEQ ID NO: 46)
-.AKVAVLGASGGIGQPLSLLLKNSPLVSRLTLYD.I (SEQ ID NO: 47) S10AB_HUMAN Protein S100-A11 GN = S100A11 PE = 1 SV = 2_1_105 P31949 M.AKISSPTETERCIESLIAVFQKYAGK.D (SEQ ID NO 48)
M.AKISSPTETERCIESLIAVFQKYAGKD.G (SEQ ID NO: 49)
D.GYNYTLSKTEFLSFMNTELAAFTKNQK.D (SEQ ID NO: 50) ANXA1_HUMAN Annexin A1 GN = ANXA1 PE = 1 SV = 2_2_346 P04083 D.ETLKKALTGHLEEVVLALLKTPAQF.D (SEQ ID NO: 51)
D.ETLKKALTGHLEEVVLALLKTPAQFD.A (SEQ ID NO: 52) ANXA3_HUMAN Annexin A3 GN = ANXA3 PE = 1 SV = 3_2_323 P12429 D.YEITLLKICGG.D (SEQ ID NO: 53) CH10_HUMAN 10 kDa heat shock protein, mitochondrial GN = HSPE1 PE = 1 SV = 2_2_102 P61604 -.AGQAFRKFLPLF.D (SEQ ID NO: 54)
-.AGQAFRKFLPLFD.R (SEQ ID NO: 55) ALBU_HUMAN Serum albumin GN = ALB PE = 1 SV = 2_25_609 P02768 D.KAACLLPKL.D (SEQ ID NO: 56)
D.KAACLLPKLD.E (SEQ ID NO: 57)
D.PHECYAKVF.D (SEQ ID NO: 58)
D.PHECYAKVFD.E (SEQ ID NO: 59)
D.KAACLLPKLDELR.D (SEQ ID NO: 60)
D.KAACLLPKLDELRD.E (SEQ ID NO: 61)
D.FVESKDVCKNYAEAKD.V (SEQ ID NO: 62) ACTA_HUMAN Actin, aortic smooth muscle GN = ACTA2 PE = 1 SV = 1_3_377 P62736 D.IKEKLCYVAL.D (SEQ ID NO: 63)
D.IKEKLCYVALD.F (SEQ ID NO: 64)
D.EAGPSIVHRKCF.- (SEQ ID NO: 65) ERH_HUMAN Enhancer of rudimentary homolog GN = ERH PE = 1 SV = 1_2_104 P84090 D.LSCLVYRA.D (SEQ ID NO: 66)
D.LSCLVYRAD.T (SEQ ID NO: 67)
D.LADLSCLVYRA.D (SEQ ID NO: 68) GBG12_HUMAN Guanine nucleotide-binding protein G (I) / G (S) / G (O) subunit gamma-12 GN = GNG12 PE = 1 SV = 3_2_69 Q9UBI6 D.PLLIGIPTSENPFKDKKTC.- (SEQ ID NO: 69) TGM2_HUMAN Protein-glutamine gamma-glutamyltransferase 2 GN = TGM2 PE = 1 SV = 2_2_687 P21980 D.ICLILL.D (SEQ ID NO: 70)
-.AEELVLERC.D (SEQ ID NO: 71)
-.AEELVLERCD.L (SEQ ID NO: 72)
D.ICLILLDVNPKFLKNAGR.D (SEQ ID NO: 73)  RAC1_HUMAN Ras-related C3 botulinum toxin substrate 1 GN = RAC1 PE = 1 SV = 1_1_189 P63000 -.MQAIKCVVVG.D (SEQ ID NO: 74) (SEQ ID NO) ATPA_HUMAN ATP synthase subunit alpha, mitochondrial GN = ATP5A1 PE = 1 SV = 1_44_553 P25705 D.AKLKEIVTNFLAGFEA.- (SEQ ID NO: 75) PHB_HUMAN Prohibitin GN = PHB PE = 1 SV = 1_1_272 P35232 D.ERVLPSITTEILKSVVARF.D (SEQ ID NO: 76)
D.ERVLPSITTEILKSVVARFD.A (SEQ ID NO: 77)
D.IVVGEGTHFLIPWVQKPIIF.D (SEQ ID NO: 78) AOFA_HUMAN Amine oxidase [flavin-containing] A GN = MAOA PE = 1 SV = 1_1_527 P21397 D.GSLPAIMGFILARKA.D (SEQ ID NO: 79) TINAL_HUMAN Tubulointerstitial nephritis antigen-like GN = TINAGL1 PE = 1 SV = 1_22_467 Q9GZM7 D.RVSIHSLGHMTPVLSPQNLLSC.D (SEQ ID NO: 80)
D.RVSIHSLGHMTPVLSPQNLLSC.D (SEQ ID NO: 81)
D.RVSIHSLGHMTPVLSPQNLLSCD.T (SEQ ID NO: 82)
D.RVSIHSLGHMTPVLSPQNLLSCD.T (SEQ ID NO: 83) APOA1_HUMAN Apolipoprotein A-I GN = APOA1 PE = 1 SV = 1_25_267 P02647 D.LRQGLLPVLESFKVSFLSALEEYTKKLNTQ.- (SEQ ID NO: 84) CH60_HUMAN 60 kDa heat shock protein, mitochondrial GN = HSPD1 PE = 1 SV = 2_27_573 P10809 D.AAGVASLLTTAEVVVTEIPKEEK.D (SEQ ID NO: 85) SODC_HUMAN Superoxide dismutase [Cu-Zn] GN = SOD1 PE = 1 SV = 2_2_154 P00441 -.ATKAVCVLKG.D (SEQ ID NO: 86)
-.ATKAVCVLKGD.G (SEQ ID NO: 87) NB5R1_HUMAN NADH-cytochrome b5 reductase 1 GN = CYB5R1 PE = 1 SV = 1_1_305 Q9UHQ9 D.PTQCFLLFANQTEK.D (SEQ ID NO: 88) HPCA_HUMAN Neuron-specific calcium-binding protein hippocalcin GN = HPCA PE = 1 SV = 2_2_193 P84074 D.PSIVRLLQC.D (SEQ ID NO: 89) S10A6_HUMAN Protein S100-A6 GN = S100A6 PE = 1 SV = 1_1_90 P06703 D.QAIGLLVAIFHKYSGREG.D (SEQ ID NO: 90) ATPD_HUMAN ATP synthase subunit delta, mitochondrial GN = ATP5D PE = 1 SV = 2_23_168 P30049 D.VPTLTGAFGILAAHVPTLQVLRPGLVVVHAE.D (SEQ ID NO: 91) CAH1_HUMAN Carbonic anhydrase 1 GN = CA1 PE = 1 SV = 2_2_261 P00915 D.GLAVIGVLMKVGEANPKLQKVL.D (SEQ ID NO: 92)  CLUS_HUMAN Clusterin GN = CLU PE = 1 SV = 1_23_449 P10909 D.VPSGVTEVVVKLF.D (SEQ ID NO: 93) MRLC2_HUMAN Myosin regulatory light chain MRLC2 GN = MYLC2B PE = 1 SV = 2_2_172 O14950 D.VIRNAFACF.D (SEQ ID NO: 94)
D.PEDVIRNAFACF.D (SEQ ID NO: 95)
D.PEDVIRNAFACFD.E (SEQ ID NO: 96) ANXA6_HUMAN Annexin A6 GN = ANXA6 PE = 1 SV = 3_2_673 P08133 D.FLKALLALCGGE.D (SEQ ID NO: 97) GPNMB_HUMAN Transmembrane glycoprotein NMB GN = GPNMB PE = 1 SV = 2_22_572 Q14956 D.LPIMFDVLIH.D (SEQ ID NO: 98) CO6A3_HUMAN Collagen alpha-3 (VI) chain GN = COL6A3 PE = 1 SV = 4_26_3177 P12111 D.SFQEVLRFVSEIVD.T (SEQ ID NO: 99)
D.PAELEQIVLSPAFILAAESLPKIG.D (SEQ ID NO: 100) LEG1_HUMAN Galectin-1 GN = LGALS1 PE = 1 SV = 2_2_135 P09382 D.FKIKCVAF.D (SEQ ID NO: 101)
D.GDFKIKCVAF.D (SEQ ID NO: 102) FIBB_HUMAN Fibrinogen beta chain GN = FGB PE = 1 SV = 2_45_491 P02675 D.SSVKPYRVYC.D (SEQ ID NO: 103)
D.SSVKPYRVYCD.M (SEQ ID NO: 104)
D.GKNYCGLPGEYWLGND.K (SEQ ID NO: 105)
D.PYKQGFGNVATNTDGKNYCGLPGEYWLGND.K (SEQ ID NO: 106) FETUA_HUMAN Alpha-2-HS-glycoprotein GN = AHSG PE = 1 SV = 1_341_367 P02765 -.TVVQPSVGAAAGPVVPPCPGRIRHFKV.- (SEQ ID NO: 107) CDC42_HUMAN Cell division control protein 42 homolog GN = CDC42 PE = 1 SV = 1_1_188 P60953 -.MQTIKCVVVG.D (SEQ ID NO: 108) TRFE_HUMAN Serotransferrin GN = TF PE = 1 SV = 2_20_698 P02787 D.EFFSEGCAPGSKK.D (SEQ ID NO: 109)
D.PQTFYYAVAVVKK.D (SEQ ID NO: 110 ANXA4_HUMAN Annexin A4 GN = ANXA4 PE = 1 SV = 4_2_319 P09525 D.YRKVLLVLCGG.D (SEQ ID NO: 111) S10AA_HUMAN Protein S100-A10 GN = S100A10 PE = 1 SV = 2_2_97 P60903 -.PSQMEHAMETMMFTFHKFAG.D (SEQ ID NO: 112)
GPSN2_HUMAN Synaptic glycoprotein SC2 GN = GPSN2 PE = 1 SV = 1_1_308 Q9NZ01 D.YPPLRMPIIPFLL.- (SEQ ID NO: 113) GBG5_HUMAN Guanine nucleotide-binding protein G (I) / G (S) / G (O) subunit gamma-5 GN = GNG5 PE = 1 SV = 3_2_65 P63218 D.PLLTGVSSSTNPFRPQKVC.- (SEQ ID NO: 114)  TLN1_HUMAN Talin-1 GN = TLN1 PE = 1 SV = 3_1_2541 Q9Y490 D.ALMQLAKAVASAAAALVLKAKSVAQRTE.D (SEQ ID NO: 115) TPP1_HUMAN Tripeptidyl-peptidase 1 GN = TPP1 PE = 1 SV = 2_196_563 O14773 D.PVTGWGTPNFPALLKTLLNP.- (SEQ ID NO: 116) THIM_HUMAN 3-ketoacyl-CoA thiolase, mitochondrial GN = ACAA2 PE = 1 SV = 2_1_397 P42765 M.ALLRGVFVVAAKRTPFGAYGGLLK.D (SEQ ID NO: 117) DHE3_HUMAN Glutamate dehydrogenase 1, mitochondrial GN = GLUD1 PE = 1 SV = 2_54_558 P00367 D.LRTAAYVNAIEKVFKVYNEAGVTFT.- (SEQ ID NO: 118) NID2_HUMAN Nidogen-2 GN = NID2 PE = 1 SV = 2_31_1375 Q14112 D.PFSKLLCWA.D (SEQ ID NO: 119)
D.PFSKLLCWAD.A (SEQ ID NO: 120) FETUA_HUMAN Alpha-2-HS-glycoprotein GN = AHSG PE = 1 SV = 1_19_300 P02765 D.GKFSVVYAKC.D (SEQ ID NO: 121) PPIB_HUMAN Peptidyl-prolyl cis-trans isomerase B GN = PPIB PE = 1 SV = 2_34_216 P23284 D.EDVGRVIFGLFGKTVPKTV.D (SEQ ID NO: 122) ATPB_HUMAN ATP synthase subunit beta, mitochondrial GN = ATP5B PE = 1 SV = 3_48_529 P06576 D.PAPATTFAHLDATTVLSRAIAELGIYPAV.D (SEQ ID NO: 123) NDUA2_HUMAN NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 GN = NDUFA2 PE = 1 SV = 3_2_99 O43678 D.LPILIRECSD.V (SEQ ID NO: 124) CLH1_HUMAN Clathrin heavy chain 1 GN = CLTC PE = 1 SV = 5_2_1675 Q00610 D.YQALRTSI.D (SEQ ID NO: 125) PGBM_HUMAN Basement membrane-specific heparan sulfate proteoglycan core protein GN = HSPG2 PE = 1 SV = 3_22_4391 P98160 D.PAAGQAAHTCFL.D (SEQ ID NO: 126) K0146_HUMAN Uncharacterized protein KIAA0146 GN = KIAA0146 PE = 2 SV = 2_1_915 Q14159 D.KTLSQLQRD.E (SEQ ID NO: 127) APOA_HUMAN Apolipoprotein (a) GN = LPA PE = 1 SV = 1_20_4548 P08519 D.SGGPLVCFEKD.K (SEQ ID NO: 128)  THIOM_HUMAN Thioredoxin, mitochondrial GN = TXN2 PE = 1 SV = 2_60_166 Q99757 D.QLEAFLKKLIG.- (SEQ ID NO: 129)

In the table, '.' Means a cleavage site, and it can be seen that it is randomly cleaved before or after aspartic acid. Also, the sequence number described next to the amino acid sequence means only an amino acid sequence between '.' Which is a cleavage site. )

Among these proteins, hemoglobin subunit beta (eg, Accession No. P6887), hemoglobin subunit gamma-1 (eg, Accession No. P69891), H3L (H3-Histone H3- like, for example, Accession No. Q6NXT2), chorionic somatomammotropin hormone (such as Accession No. P01243), vitronectin (Accession No. P04004), fibronectin (such as Accession No. P02751), peptides derived from Annexin A5 (e.g., Accession No. P08758), and Annexin A2 (e.g., Accession No. P07355) have a high proportion of the peptides in the overall mixture, In addition, there is a high probability of affecting the growth and differentiation of stem cells, such as secretory protein, growth factor, extracellular matrix protein.

Thus, the peptide mixture according to the present invention is hemoglobin subunit beta (e.g. Accession No. P6887), hemoglobin subunit gamma-1 (e.g. Accession No. P69891), H3L (H3). Histone H3-like, such as Accession No. Q6NXT2), chorionic somatomammotropin hormone such as Accession No. P01243, Vitronectin, Accession No. P04004, Fibronectin Amino acids of one or more proteins selected from the group consisting of, for example, Accession No. P02751), Annexin A5 (eg, Accession No. P08758), and Annexin A2 (eg, Accession No. P07355) It is preferred to include essentially peptides having 7-40, preferably 7-30 amino acids in sequence.

For example, the peptide mixture according to the present invention may include essentially one or more selected from the group consisting of peptides having amino acid sequences of SEQ ID NOs: 1 to 34.

Another example of the present invention provides a method of preparing a placental derived peptide mixture from the placenta. The preparation method may include hydrolyzing the placenta with an acid solution of pH 2 to 3 at 95 to 105 ° C. for 1 to 4 hours. The acid may be at least one weak acid selected from the group consisting of acetic acid, trifluoroacetic acid (TFA) and formic acid.

According to a preferred embodiment of the present invention, impurities may be removed through one or more processes selected from the group consisting of centrifugation, lyophilization, and the like following the hydrolysis step.

For example, the preparation method further comprises the step of centrifuging the hydrolyzate obtained by treatment with the weak acid of pH 2 to 3 to take a supernatant, to remove impurities or undigested protein that may be included in the hydrolyzate. Can be removed The centrifugation conditions are not particularly limited and may be performed at 2500-3500xg for 5 minutes to 20 minutes.

In addition, the obtained hydrolyzate or supernatant may further comprise the step of lyophilizing to remove the acid.

In one embodiment, when the centrifugation process and the lyophilization process are sequentially performed, the supernatant of the peptide extract is recovered by centrifugation (2500-3500xg, 1 minute to 30 minutes) after hydrolysis, and Lyophilization to remove the acid and purified water was added to adjust the concentration of the peptide mixture to about 3-4 mg / ml and filtered with a 0.1 to 0.3 um membrane filter, to the filtrate was added a conventional preservative and 10 minutes at 100 to 130 ℃ It can be autoclaved at high temperature for 40 minutes.

The placenta-derived peptide mixture according to the present invention was found to have an activity of promoting differentiation of stem cells, such as bone marrow-derived mesenchymal stem cells, into osteoblasts (see FIGS. 2 and 3a and 3b).

Therefore, another example of the present invention provides a composition for inducing bone differentiation of stem cells comprising the placental peptide mixture as an active ingredient. Another example of the present invention provides a method for inducing bone differentiation of stem cells comprising culturing stem cells, such as mesenchymal stem cells isolated from bone marrow, re-blood cells or adipocytes, with the placental peptide mixture.

More specifically, the method for inducing bone differentiation of stem cells comprises the steps of isolating mesenchymal stem cells from bone marrow, re-blood cells or adipocytes, and culturing the isolated mesenchymal stem cells with the placenta-derived peptide mixture. It may be to include. The step of culturing with the placental peptide mixture may be carried out by culturing the isolated mesenchymal stem cells in differentiation induction medium containing the placental peptide mixture. The differentiation induction medium is not particularly limited, and may be used all of the differentiation induction medium of stem cells that are commonly used, for example, DMEM (Dulbecco's Modified Eagle Medium), FBS (fetal bovine serum), betaglycerophosphate (β- glycerophosphate), 100nM dexamethasone (Dexamethasone), ascorbate-2-phosphate (Ascorbate-2-phosphate) may be one or more selected from the group consisting of. The content of the placental peptide mixture contained in the differentiation-inducing medium is not particularly limited, but in order to obtain sufficient bone differentiation effect, 0.1 to 100 ug per 100 ul of differentiation-inducing medium, preferably 0.5 to 50 ug, more preferably It is good that it is 1-20ug.

By the above-described bone differentiation inducing effect, the placental peptide mixture according to the present invention can be usefully used for the prevention, improvement, reduction and / or treatment of bone regeneration and / or various bone diseases. Accordingly, another example of the present invention provides a composition for bone regeneration or a composition for preventing, improving, alleviating and / or treating a bone disease comprising the placental peptide mixture as an active ingredient.

The bone disease may be selected from the group consisting of osteoporosis, bone dysplasia, fracture, osteomalacia, Paget's disease, periodontal disease, and the like.

There is no particular limitation on the manner of administration of the composition for bone regeneration and / or the composition for the prevention, alleviation or treatment of bone diseases according to the present invention. . The dosage of the composition for bone regeneration and / or the composition for preventing, improving, reducing and / or treating bone diseases according to the present invention may vary depending on the age, weight, sex, dosage form, health condition, type of disease and symptoms of the patient. have. For example, in order to obtain sufficient bone regeneration and / or bone disease prevention, improvement, alleviation or therapeutic effect, the dosage of the composition may be 0.05 to 2 mL, but is not limited thereto .

By placenta-derived peptide mixture production technology from the placenta according to the present invention, a peptide mixture can be obtained which is distinguished from the existing placental hydrolyzate, in which the protein is completely degraded and is present in the amino acid state. By acting as an active ingredient, it is possible to prepare a placental-derived peptide mixture exerting new effects, such as osteoinduction, and thus can be usefully used for the treatment of bone regeneration and bone diseases.

Hereinafter, the present invention will be described in more detail. However, the following examples are only for illustrating the present invention, but the scope of the present invention is not limited to these examples.

Example 1 Preparation of Placental-Derived Peptide Mixtures

The mother's placental placenta was washed several times with physiological saline, cut, and dissolved 1 g of lyophilized chorionic tissue in 50 mL of 15% (v / v) acetic acid solution (pH 2.5), followed by hydrolysis at 95 ° C. for 2 hours. It was. The above conditions are designed to specifically act on only aspartic acid among the amino acids constituting the protein to cause a hydrolysis reaction.

The obtained hydrolysis solution was centrifuged (3,000xg, 15 minutes), the supernatant was collected, lyophilized to remove acid, dissolved in 10 mL of purified water or 0.1% (v / v) acetic acid solution, and then 0.22um membrane filter (Millipore, USA), and sterilized for 15 minutes at 105 ℃ in a high temperature and high pressure sterilizer (Autoclave SP510, Yamato, Japan). Through the above procedure, a peptide mixture of 30 to 40 mg was obtained from 1 g of lyophilized placenta.

Peptide mixtures extracted from the placenta were separated according to molecular weight using SDS-PAGE, and stained with Coomassie Brilliant Blue to confirm the distribution of the molecular weight. The results are shown in FIG. As can be seen in Figure 1, the placental hydrolyzate obtained in this example is in the form of a mixture of various peptides predominantly consisting of peptides of about 4,000 ~ 5,000 Da molecular weight (Lane 3), the existing placenta extract (Lane 1, melamine, Savior) Pharmaceutical) and human half-hydrolyzate (Lane 2, Lycon, Savior Pharmaceuticals) can be seen that the difference in the molecular weight distribution.

< Example  2> placenta-derived Peptide  Analysis of the components of the mixture

The placental derived peptide mixture obtained in Example 1 was isolated with an Agilent 1100 Nanoflow System (Agilent Technologies) and sequenced with a linked QSTAR-XL mass spectrometer (Applied Biosystems). Peptide binding and chromatographic separation were performed using a 10 cm silica emitter (75 m inside diameter) filled with reverse phase C18 resin (Agilent Technologies), and the sample loading of the peptide was 15 μl / min with an autosampler. Peptides were separated at a rate of 0.3 μl / min using C18-filled nanocolumns (length 100 mm), and the mobile phase used was 0% (v / v) in 0.1% (v / v) formic acid. Different gradients of (A) and 100% (v / v) (B) of acetonitrile (B 3-15% (v / v) for 0-10 minutes, B 15-20 for 10-15 minutes) % (v / v), B 20-32.5% (v / v) for 15-105 minutes, B 32.5-45% (v / v) for 105-120 minutes, B 45- for 120-125 minutes It was raised to 90% (v / v) and washed with the final 90% (v / v)).

The eluted peptides were electrosprayed and introduced directly into the mass spectrometer. The mass spectrometry software used Mascot program (version, 2.1) to automatically analyze MS and MS / MS according to the data. The obtained result is shown below. As can be seen from the results below, the presence of about 60 human protein-derived peptides, such as secreted proteins such as albumin, extracellular matrix protein, growth hormone, histone, etc. As can be seen that hydrolysis occurred at the amino or carboxy terminus of aspartic acid.

The results obtained from this analysis are as follows:

Example 3 Effect of Placental-Derived Peptide Mixture on Stem Cell Differentiation

Dispense 10000 bone marrow-derived mesenchymal stem cells into 96-well plates for growth medium (15% fetal bovine serum (GIBCO, USA), DMEM (BioWhittaker, USA), 50 U / ml penicillin, and 50 ug / ml streptomycin (Invitrogen, USA)) and after 24 hours, the growth medium is newly exchanged, and after 48 hours it is exchanged with differentiation-inducing medium (0.1M dexamethasone, 50uM ascorbate-2-phosphate, 10mM β-glycerophosphate added growth medium) I gave it. Placenta-derived peptide mixture was put together in differentiation-inducing medium (2.5ug, 5ug, 10ug of placenta-derived peptide mixture was added per 100ul of differentiation-inducing medium, respectively).

Differentiation induction medium was exchanged every 3 days to monitor the differentiation process. After 12 days of differentiation, minerals were deposited on an extracellular matrix (ECM). The results are shown in FIG. 2. Alizarin red staining was also used to measure the degree of differentiation into osteoblasts. Wipe the cells twice with PBS (Phosphate-buffered saline), react for 15 minutes at room temperature in the presence of 4% paraformaldehyde, fix the cells, wash three times with purified water, and remove 100ul Alizarin red solution (1% Alizarin Red (sigma, A5533). )) Was added and reacted for 20 minutes. After removing the Alizarin red solution, it was washed 5 times with purified water (scanned to obtain an image at this stage), and 100% of 10% acetic acid solution was added to the well and allowed to react for 30 minutes. After vortexing strongly for 30 seconds and reacting for 30 minutes in a dry oven at 60 ° C. (gluing a sealing sticker to prevent evaporation), 10ul ammonium hydroxide was added to each well by 7ul, and the absorbance was measured at 405nm. The results obtained are shown in FIGS. 3A and 3B.

As can be seen in Figures 2 and 3a and 3b, it can be seen that the placental-derived peptide mixture has an activity of inducing differentiation of mesenchymal stem cells into osteoblasts.

Figure 1 shows the results of analyzing the molecular weight distribution of the placenta-derived peptide mixture obtained in Example 1 via SDS-PAGE (Lane 1: placenta extract, melamine (Suju Pharmaceutical), Lane 2: placenta hydrolysates, lycones (European Pharmaceuticals), Lane 3: Placental-derived peptide mixture of Example 1).

Figure 2 is an optical micrograph showing the effect of promoting the differentiation of mesenchymal stem cells into osteoblasts by the placental-derived peptide mixture obtained in Example 1 (1) mesenchymal stem cells maintained in the growth medium for 12 days; Mesenchymal stem cells cultured in medium for 12 days; ③ Mesenchymal stem cells cultured for 12 days in differentiation-inducing medium containing 2.5ug placenta-derived peptide mixture; ④ Differentiation-inducing medium containing 5ug placenta-derived peptide mixture for 12 days Cultured mesenchymal stem cells ⑤ Mesenchymal stem cells cultured for 12 days in differentiation-inducing medium containing 10ug placenta-derived peptide mixture).

Figure 3a and 3b shows the effect of promoting the differentiation of mesenchymal stem cells into osteoblasts by the placental-derived peptide mixture obtained in Example 1, 3a shows the results of Alizarin red staining image scan ((1): growth (2): Mesenchymal stem cells (triplicate) incubated for 12 days in differentiation-inducing medium (3): 12 days in differentiation-inducing medium containing placental-derived peptide mixture Cultured mesenchymal stem cells from the left peptide content of 2.5ug, 5ug, 10ug), 3b shows the change in absorbance.

<110> Sigmol, Inc. <120> Peptide mixture extracted from human placenta, and preparation          method and use <160> 129 <170> KopatentIn 1.71 <210> 1 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBB_HUMAN <400> 1 Asn Leu Lys Gly Thr Phe Ala Thr Leu Ser Glu Leu His Cys   1 5 10 <210> 2 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBB_HUMAN <400> 2 Asn Leu Lys Gly Thr Phe Ala Thr Leu Ser Glu Leu His Cys Asp   1 5 10 15 <210> 3 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBB_HUMAN <400> 3 Asn Leu Lys Gly Thr Phe Ala Thr Leu Ser Glu Leu His Cys Asp Lys   1 5 10 15 Leu his val             <210> 4 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBB_HUMAN <400> 4 Gly Leu Ala His Leu Asp Asn Leu Lys Gly Thr Phe Ala Thr Leu Ser   1 5 10 15 Glu leu his cys              20 <210> 5 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBB_HUMAN <400> 5 Asn Leu Lys Gly Thr Phe Ala Thr Leu Ser Glu Leu His Cys Asp Lys   1 5 10 15 Leu His Val Asp              20 <210> 6 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBB_HUMAN <400> 6 Gly Leu Ala His Leu Asp Asn Leu Lys Gly Thr Phe Ala Thr Leu Ser   1 5 10 15 Glu Leu His Cys Asp              20 <210> 7 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBB_HUMAN <400> 7 Gly Leu Ala His Leu Asp Asn Leu Lys Gly Thr Phe Ala Thr Leu Ser   1 5 10 15 Glu Leu His Cys Asp Lys Leu His Val              20 25 <210> 8 <211> 26 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBB_HUMAN <400> 8 Gly Leu Ala His Leu Asp Asn Leu Lys Gly Thr Phe Ala Thr Leu Ser   1 5 10 15 Glu Leu His Cys Asp Lys Leu His Val Asp              20 25 <210> 9 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBG1_HUMAN <400> 9 Leu Lys Gly Thr Phe Ala Gln Leu Ser Glu Leu His Cys   1 5 10 <210> 10 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBG1_HUMAN <400> 10 Asp Leu Lys Gly Thr Phe Ala Gln Leu Ser Glu Leu His Cys   1 5 10 <210> 11 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBG1_HUMAN <400> 11 Leu Lys Gly Thr Phe Ala Gln Leu Ser Glu Leu His Cys Asp   1 5 10 <210> 12 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBG1_HUMAN <400> 12 Leu Lys Gly Thr Phe Ala Gln Leu Ser Glu Leu His Cys Asp Lys Leu   1 5 10 15 His val         <210> 13 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBG1_HUMAN <400> 13 Leu Lys Gly Thr Phe Ala Gln Leu Ser Glu Leu His Cys Asp Lys Leu   1 5 10 15 His Val Asp             <210> 14 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBG1_HUMAN <400> 14 Ala Gly Gly Glu Thr Leu Gly Arg Leu Leu Val Val Tyr Pro Trp Thr   1 5 10 15 Gln Arg Phe Phe              20 <210> 15 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBG1_HUMAN <400> 15 Ala Gly Gly Glu Thr Leu Gly Arg Leu Leu Val Val Tyr Pro Trp Thr   1 5 10 15 Gln Arg Phe Phe Asp              20 <210> 16 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from H3L_HUMAN <400> 16 Thr Asn Leu Cys Ala Ile His Ala Lys Arg Val Thr Ile Met Pro Lys   1 5 10 15 <210> 17 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from H3L_HUMAN <400> 17 Thr Asn Leu Cys Ala Ile His Ala Lys Arg Val Thr Ile Met Pro Lys   1 5 10 15 Asp     <210> 18 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CSH_HUMAN <400> 18 Ala Leu Leu Lys Asn Tyr Gly Leu Leu Tyr Cys Phe Arg Lys   1 5 10 <210> 19 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CSH_HUMAN <400> 19 Ala Leu Leu Lys Asn Tyr Gly Leu Leu Tyr Cys Phe Arg Lys Asp   1 5 10 15 <210> 20 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CSH_HUMAN <400> 20 Ala Leu Leu Lys Asn Tyr Gly Leu Leu Tyr Cys Phe Arg Lys Asp Met   1 5 10 15 <210> 21 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from VTNC_HUMAN <400> 21 Pro Pro Tyr Pro Arg Ser Ile Ala Gln Tyr Trp Leu Gly Cys Pro Ala   1 5 10 15 Pro Gly His Leu              20 <210> 22 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from FINC_HUMAN <400> 22 Tyr Thr Ile Thr Val Tyr Ala Val Thr Gly Arg Gly   1 5 10 <210> 23 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from FINC_HUMAN <400> 23 Thr Ser Glu Tyr Ile Ile Ser Cys His Pro Val Gly Thr   1 5 10 <210> 24 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from FINC_HUMAN <400> 24 Thr Ser Glu Tyr Ile Ile Ser Cys His Pro Val Gly Thr Asp   1 5 10 <210> 25 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA5_HUMAN <400> 25 Tyr Lys Lys Ala Leu Leu Leu Leu Cys Gly Glu   1 5 10 <210> 26 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA5_HUMAN <400> 26 Tyr Lys Lys Ala Leu Leu Leu Leu Cys Gly Glu Asp   1 5 10 <210> 27 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA5_HUMAN <400> 27 Thr Ser Gly Asp Tyr Lys Lys Ala Leu Leu Leu Leu Cys Gly Glu   1 5 10 15 <210> 28 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA5_HUMAN <400> 28 Leu Lys Ser Glu Leu Thr Gly Lys Phe Glu Lys Leu Ile Val Ala Leu   1 5 10 15 Met Lys Pro Ser Arg Leu Tyr              20 <210> 29 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA2_HUMAN <400> 29 Tyr Gln Lys Ala Leu Leu Tyr Leu Cys Gly Gly   1 5 10 <210> 30 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA2_HUMAN <400> 30 Tyr Gln Lys Ala Leu Leu Tyr Leu Cys Gly Gly Asp   1 5 10 <210> 31 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA2_HUMAN <400> 31 Ser Thr Val His Glu Ile Leu Cys Lys Leu Ser Leu Glu Gly   1 5 10 <210> 32 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA2_HUMAN <400> 32 Thr Lys Gly Asp Tyr Gln Lys Ala Leu Leu Tyr Leu Cys Gly Gly   1 5 10 15 <210> 33 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA2_HUMAN <400> 33 Ser Thr Val His Glu Ile Leu Cys Lys Leu Ser Leu Glu Gly Asp   1 5 10 15 <210> 34 <211> 32 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA2_HUMAN <400> 34 Ser Thr Val His Glu Ile Leu Cys Lys Leu Ser Leu Glu Gly Asp His   1 5 10 15 Ser Thr Pro Pro Ser Ala Tyr Gly Ser Val Lys Ala Tyr Thr Asn Phe              20 25 30 <210> 35 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ACTB_HUMAN <400> 35 Ile Lys Glu Lys Leu Cys Tyr Val Ala Leu   1 5 10 <210> 36 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ACTB_HUMAN <400> 36 Ile Lys Glu Lys Leu Cys Tyr Val Ala Leu Asp   1 5 10 <210> 37 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ACTB_HUMAN <400> 37 Glu Ser Gly Pro Ser Ile Val His Arg Lys Cys Phe   1 5 10 <210> 38 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from IGHG3_HUMAN <400> 38 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val   1 5 10 15 <210> 39 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from IGHG3_HUMAN <400> 39 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp   1 5 10 15 <210> 40 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from IGHG3_HUMAN <400> 40 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp   1 5 10 15 Val Ser His Glu              20 <210> 41 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBA_HUMAN <400> 41 Lys Phe Leu Ala Ser Val Ser Thr Val Leu Thr Ser Lys Tyr Arg   1 5 10 15 <210> 42 <211> 31 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBA_HUMAN <400> 42 Pro Val Asn Phe Lys Leu Leu Ser His Cys Leu Leu Val Thr Leu Ala   1 5 10 15 Ala His Leu Pro Ala Glu Phe Thr Pro Ala Val His Ala Ser Leu              20 25 30 <210> 43 <211> 32 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HBA_HUMAN <400> 43 Pro Val Asn Phe Lys Leu Leu Ser His Cys Leu Leu Val Thr Leu Ala   1 5 10 15 Ala His Leu Pro Ala Glu Phe Thr Pro Ala Val His Ala Ser Leu Asp              20 25 30 <210> 44 <211> 28 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from MDHM_HUMAN <400> 44 Pro Ala Arg Val Asn Val Pro Val Ile Gly Gly His Ala Gly Lys Thr   1 5 10 15 Ile Ile Pro Leu Ile Ser Gln Cys Thr Pro Lys Val              20 25 <210> 45 <211> 29 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from MDHM_HUMAN <400> 45 Pro Ala Arg Val Asn Val Pro Val Ile Gly Gly His Ala Gly Lys Thr   1 5 10 15 Ile Ile Pro Leu Ile Ser Gln Cys Thr Pro Lys Val Asp              20 25 <210> 46 <211> 32 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from MDHM_HUMAN <400> 46 Ala Lys Val Ala Val Leu Gly Ala Ser Gly Gly Ile Gly Gln Pro Leu   1 5 10 15 Ser Leu Leu Leu Lys Asn Ser Pro Leu Val Ser Arg Leu Thr Leu Tyr              20 25 30 <210> 47 <211> 33 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from MDHM_HUMAN <400> 47 Ala Lys Val Ala Val Leu Gly Ala Ser Gly Gly Ile Gly Gln Pro Leu   1 5 10 15 Ser Leu Leu Leu Lys Asn Ser Pro Leu Val Ser Arg Leu Thr Leu Tyr              20 25 30 Asp     <210> 48 <211> 26 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from S10AB_HUMAN <400> 48 Ala Lys Ile Ser Ser Pro Thr Glu Thr Glu Arg Cys Ile Glu Ser Leu   1 5 10 15 Ile Ala Val Phe Gln Lys Tyr Ala Gly Lys              20 25 <210> 49 <211> 27 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from S10AB_HUMAN <400> 49 Ala Lys Ile Ser Ser Pro Thr Glu Thr Glu Arg Cys Ile Glu Ser Leu   1 5 10 15 Ile Ala Val Phe Gln Lys Tyr Ala Gly Lys Asp              20 25 <210> 50 <211> 27 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from S10AB_HUMAN <400> 50 Gly Tyr Asn Tyr Thr Leu Ser Lys Thr Glu Phe Leu Ser Phe Met Asn   1 5 10 15 Thr Glu Leu Ala Ala Phe Thr Lys Asn Gln Lys              20 25 <210> 51 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA1_HUMAN <400> 51 Glu Thr Leu Lys Lys Ala Leu Thr Gly His Leu Glu Glu Val Val Leu   1 5 10 15 Ala Leu Leu Lys Thr Pro Ala Gln Phe              20 25 <210> 52 <211> 26 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA1_HUMAN <400> 52 Glu Thr Leu Lys Lys Ala Leu Thr Gly His Leu Glu Glu Val Val Leu   1 5 10 15 Ala Leu Leu Lys Thr Pro Ala Gln Phe Asp              20 25 <210> 53 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA3_HUMAN <400> 53 Tyr Glu Ile Thr Leu Leu Lys Ile Cys Gly Gly   1 5 10 <210> 54 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CH10_HUMAN <400> 54 Ala Gly Gln Ala Phe Arg Lys Phe Leu Pro Leu Phe   1 5 10 <210> 55 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> CH10_HUMAN <400> 55 Ala Gly Gln Ala Phe Arg Lys Phe Leu Pro Leu Phe Asp   1 5 10 <210> 56 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ALBU_HUMAN <400> 56 Lys Ala Ala Cys Leu Leu Pro Lys Leu   1 5 <210> 57 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ALBU_HUMAN <400> 57 Lys Ala Ala Cys Leu Leu Pro Lys Leu Asp   1 5 10 <210> 58 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ALBU_HUMAN <400> 58 Pro His Glu Cys Tyr Ala Lys Val Phe   1 5 <210> 59 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ALBU_HUMAN <400> 59 Pro His Glu Cys Tyr Ala Lys Val Phe Asp   1 5 10 <210> 60 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ALBU_HUMAN <400> 60 Lys Ala Ala Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg   1 5 10 <210> 61 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ALBU_HUMAN <400> 61 Lys Ala Ala Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp   1 5 10 <210> 62 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ALBU_HUMAN <400> 62 Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp   1 5 10 15 <210> 63 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ACTA_HUMAN <400> 63 Ile Lys Glu Lys Leu Cys Tyr Val Ala Leu   1 5 10 <210> 64 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ACTA_HUMAN <400> 64 Ile Lys Glu Lys Leu Cys Tyr Val Ala Leu Asp   1 5 10 <210> 65 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ACTA_HUMAN <400> 65 Glu Ala Gly Pro Ser Ile Val His Arg Lys Cys Phe   1 5 10 <210> 66 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ERH_HUMAN <400> 66 Leu Ser Cys Leu Val Tyr Arg Ala   1 5 <210> 67 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ERH_HUMAN <400> 67 Leu Ser Cys Leu Val Tyr Arg Ala Asp   1 5 <210> 68 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ERH_HUMAN <400> 68 Leu Ala Asp Leu Ser Cys Leu Val Tyr Arg Ala   1 5 10 <210> 69 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from GBG12_HUMAN <400> 69 Pro Leu Leu Ile Gly Ile Pro Thr Ser Glu Asn Pro Phe Lys Asp Lys   1 5 10 15 Lys Thr Cys             <210> 70 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TGM2_HUMAN <400> 70 Ile Cys Leu Ile Leu Leu   1 5 <210> 71 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TGM2_HUMAN <400> 71 Ala Glu Glu Leu Val Leu Glu Arg Cys   1 5 <210> 72 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TGM2_HUMAN <400> 72 Ala Glu Glu Leu Val Leu Glu Arg Cys Asp   1 5 10 <210> 73 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TGM2_HUMAN <400> 73 Ile Cys Leu Ile Leu Leu Asp Val Asn Pro Lys Phe Leu Lys Asn Ala   1 5 10 15 Gly arg         <210> 74 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from RAC1_HUMAN <400> 74 Met Gln Ala Ile Lys Cys Val Val Val Gly   1 5 10 <210> 75 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ATPA_HUMAN <400> 75 Ala Lys Leu Lys Glu Ile Val Thr Asn Phe Leu Ala Gly Phe Glu Ala   1 5 10 15 <210> 76 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from PHB_HUMAN <400> 76 Glu Arg Val Leu Pro Ser Ile Thr Thr Glu Ile Leu Lys Ser Val Val   1 5 10 15 Ala Arg Phe             <210> 77 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from PHB_HUMAN <400> 77 Glu Arg Val Leu Pro Ser Ile Thr Thr Glu Ile Leu Lys Ser Val Val   1 5 10 15 Ala Arg Phe Asp              20 <210> 78 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from PHB_HUMAN <400> 78 Ile Val Val Gly Glu Gly Thr His Phe Leu Ile Pro Trp Val Gln Lys   1 5 10 15 Pro Ile Ile Phe              20 <210> 79 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from AOFA_HUMAN <400> 79 Gly Ser Leu Pro Ala Ile Met Gly Phe Ile Leu Ala Arg Lys Ala   1 5 10 15 <210> 80 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TINAL_HUMAN <400> 80 Arg Val Ser Ile His Ser Leu Gly His Met Thr Pro Val Leu Ser Pro   1 5 10 15 Gln Asn Leu Leu Ser Cys              20 <210> 81 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TINAL_HUMAN <400> 81 Arg Val Ser Ile His Ser Leu Gly His Met Thr Pro Val Leu Ser Pro   1 5 10 15 Gln Asn Leu Leu Ser Cys              20 <210> 82 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TINAL_HUMAN <400> 82 Arg Val Ser Ile His Ser Leu Gly His Met Thr Pro Val Leu Ser Pro   1 5 10 15 Gln Asn Leu Leu Ser Cys Asp              20 <210> 83 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TINAL_HUMAN <400> 83 Arg Val Ser Ile His Ser Leu Gly His Met Thr Pro Val Leu Ser Pro   1 5 10 15 Gln Asn Leu Leu Ser Cys Asp              20 <210> 84 <211> 30 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from APOA1_HUMAN <400> 84 Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe   1 5 10 15 Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln              20 25 30 <210> 85 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CH60_HUMAN <400> 85 Ala Ala Gly Val Ala Ser Leu Leu Thr Thr Ala Glu Val Val Val Thr   1 5 10 15 Glu Ile Pro Lys Glu Glu Lys              20 <210> 86 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from SODC_HUMAN <400> 86 Ala Thr Lys Ala Val Cys Val Leu Lys Gly   1 5 10 <210> 87 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from SODC_HUMAN <400> 87 Ala Thr Lys Ala Val Cys Val Leu Lys Gly Asp   1 5 10 <210> 88 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from NB5R1_HUMAN <400> 88 Pro Thr Gln Cys Phe Leu Leu Phe Ala Asn Gln Thr Glu Lys   1 5 10 <210> 89 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from HPCA_HUMAN <400> 89 Pro Ser Ile Val Arg Leu Leu Gln Cys   1 5 <210> 90 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from S10A6_HUMAN <400> 90 Gln Ala Ile Gly Leu Leu Val Ala Ile Phe His Lys Tyr Ser Gly Arg   1 5 10 15 Glu gly         <210> 91 <211> 31 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ATPD_HUMAN <400> 91 Val Pro Thr Leu Thr Gly Ala Phe Gly Ile Leu Ala Ala His Val Pro   1 5 10 15 Thr Leu Gln Val Leu Arg Pro Gly Leu Val Val Val His Ala Glu              20 25 30 <210> 92 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CAH1_HUMAN <400> 92 Gly Leu Ala Val Ile Gly Val Leu Met Lys Val Gly Glu Ala Asn Pro   1 5 10 15 Lys Leu Gln Lys Val Leu              20 <210> 93 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CLUS_HUMAN <400> 93 Val Pro Ser Gly Val Thr Glu Val Val Val Lys Leu Phe   1 5 10 <210> 94 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from MRLC2_HUMAN <400> 94 Val Ile Arg Asn Ala Phe Ala Cys Phe   1 5 <210> 95 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from MRLC2_HUMAN <400> 95 Pro Glu Asp Val Ile Arg Asn Ala Phe Ala Cys Phe   1 5 10 <210> 96 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from MRLC2_HUMAN <400> 96 Pro Glu Asp Val Ile Arg Asn Ala Phe Ala Cys Phe Asp   1 5 10 <210> 97 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA6_HUMAN <400> 97 Phe Leu Lys Ala Leu Leu Ala Leu Cys Gly Gly Glu   1 5 10 <210> 98 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from GPNMB_HUMAN <400> 98 Leu Pro Ile Met Phe Asp Val Leu Ile His   1 5 10 <210> 99 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CO6A3_HUMAN <400> 99 Ser Phe Gln Glu Val Leu Arg Phe Val Ser Glu Ile Val Asp   1 5 10 <210> 100 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CO6A3_HUMAN <400> 100 Pro Ala Glu Leu Glu Gln Ile Val Leu Ser Pro Ala Phe Ile Leu Ala   1 5 10 15 Ala Glu Ser Leu Pro Lys Ile Gly              20 <210> 101 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from LEG1_HUMAN <400> 101 Phe Lys Ile Lys Cys Val Ala Phe   1 5 <210> 102 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from LEG1_HUMAN <400> 102 Gly Asp Phe Lys Ile Lys Cys Val Ala Phe   1 5 10 <210> 103 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from FIBB_HUMAN <400> 103 Ser Ser Val Lys Pro Tyr Arg Val Tyr Cys   1 5 10 <210> 104 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from FIBB_HUMAN <400> 104 Ser Ser Val Lys Pro Tyr Arg Val Tyr Cys Asp   1 5 10 <210> 105 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from FIBB_HUMAN <400> 105 Gly Lys Asn Tyr Cys Gly Leu Pro Gly Glu Tyr Trp Leu Gly Asn Asp   1 5 10 15 <210> 106 <211> 30 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from FIBB_HUMAN <400> 106 Pro Tyr Lys Gln Gly Phe Gly Asn Val Ala Thr Asn Thr Asp Gly Lys   1 5 10 15 Asn Tyr Cys Gly Leu Pro Gly Glu Tyr Trp Leu Gly Asn Asp              20 25 30 <210> 107 <211> 27 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from FETUA_HUMAN <400> 107 Thr Val Val Gln Pro Ser Val Gly Ala Ala Ala Gly Pro Val Val Pro   1 5 10 15 Pro Cys Pro Gly Arg Ile Arg His Phe Lys Val              20 25 <210> 108 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CDC42_HUMAN <400> 108 Met Gln Thr Ile Lys Cys Val Val Val Gly   1 5 10 <210> 109 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TRFE_HUMAN <400> 109 Glu Phe Phe Ser Glu Gly Cys Ala Pro Gly Ser Lys Lys   1 5 10 <210> 110 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TRFE_HUMAN <400> 110 Pro Gln Thr Phe Tyr Tyr Ala Val Ala Val Val Lys Lys   1 5 10 <210> 111 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ANXA4_HUMAN <400> 111 Tyr Arg Lys Val Leu Leu Val Leu Cys Gly Gly   1 5 10 <210> 112 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from S10AA_HUMAN <400> 112 Pro Ser Gln Met Glu His Ala Met Glu Thr Met Met Phe Thr Phe His   1 5 10 15 Lys Phe Ala Gly              20 <210> 113 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from GPSN2_HUMAN <400> 113 Tyr Pro Pro Leu Arg Met Pro Ile Ile Pro Phe Leu Leu   1 5 10 <210> 114 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from GBG5_HUMAN <400> 114 Pro Leu Leu Thr Gly Val Ser Ser Ser Thr Asn Pro Phe Arg Pro Gln   1 5 10 15 Lys val cys             <210> 115 <211> 28 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TLN1_HUMAN <400> 115 Ala Leu Met Gln Leu Ala Lys Ala Val Ala Ser Ala Ala Ala Ala Leu   1 5 10 15 Val Leu Lys Ala Lys Ser Val Ala Gln Arg Thr Glu              20 25 <210> 116 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from TPP1_HUMAN <400> 116 Pro Val Thr Gly Trp Gly Thr Pro Asn Phe Pro Ala Leu Leu Lys Thr   1 5 10 15 Leu Leu Asn Pro              20 <210> 117 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from THIM_HUMAN <400> 117 Ala Leu Leu Arg Gly Val Phe Val Val Ala Ala Lys Arg Thr Pro Phe   1 5 10 15 Gly Ala Tyr Gly Gly Leu Leu Lys              20 <210> 118 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from DHE3_HUMAN <400> 118 Leu Arg Thr Ala Ala Tyr Val Asn Ala Ile Glu Lys Val Phe Lys Val   1 5 10 15 Tyr Asn Glu Ala Gly Val Thr Phe Thr              20 25 <210> 119 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from NID2_HUMAN <400> 119 Pro Phe Ser Lys Leu Leu Cys Trp Ala   1 5 <210> 120 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from NID2_HUMAN <400> 120 Pro Phe Ser Lys Leu Leu Cys Trp Ala Asp   1 5 10 <210> 121 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from FETUA_HUMAN <400> 121 Gly Lys Phe Ser Val Val Tyr Ala Lys Cys   1 5 10 <210> 122 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from PPIB_HUMAN <400> 122 Glu Asp Val Gly Arg Val Ile Phe Gly Leu Phe Gly Lys Thr Val Pro   1 5 10 15 Lys thr val             <210> 123 <211> 29 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from ATPB_HUMAN <400> 123 Pro Ala Pro Ala Thr Thr Phe Ala His Leu Asp Ala Thr Thr Val Leu   1 5 10 15 Ser Arg Ala Ile Ala Glu Leu Gly Ile Tyr Pro Ala Val              20 25 <210> 124 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from NDUA2_HUMAN <400> 124 Leu Pro Ile Leu Ile Arg Glu Cys Ser Asp   1 5 10 <210> 125 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from CLH1_HUMAN <400> 125 Tyr Gln Ala Leu Arg Thr Ser Ile   1 5 <210> 126 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from PGBM_HUMAN <400> 126 Pro Ala Ala Gly Gln Ala Ala His Thr Cys Phe Leu   1 5 10 <210> 127 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from K0146_HUMAN <400> 127 Lys Thr Leu Ser Gln Leu Gln Arg Asp   1 5 <210> 128 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from APOA_HUMAN <400> 128 Ser Gly Gly Pro Leu Val Cys Phe Glu Lys Asp   1 5 10 <210> 129 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide derived from THIOM_HUMAN <400> 129 Gln Leu Glu Ala Phe Leu Lys Lys Leu Ile Gly   1 5 10  

Claims (14)

The placenta is obtained by hydrolysis at 95-105 ° C. with an acid solution of pH 2-3, The acid is at least one selected from the group consisting of acetic acid, trifluoroacetic acid (TFA), and formic acid, Placental Peptide Mixture. The method of claim 1, The placenta is a placenta or placenta derived peptide mixture. The method of claim 1, Placenta-derived peptide mixture comprising peptides consisting of contiguous 7-40 amino acids in the amino acid sequence of one or more proteins selected from the group consisting of the following proteins: Hemoglobin subunit beta (Accession No. P6887), Hemoglobin subunit gamma-1, Accession No. P69891, H3L (H3-Histone H3-like, Accession No. Q6NXT2), villi Chorionic somatomammotropin hormone (Accession No. P01243), Vitronectin, Accession No. P04004, Fibronectin (Fibronectin, Accession No. P02751), Annexin A5 (Annexin A5, Accession No. P08758) ), Annexin A2 (Annexin A2, Accession No. P07355), ACTB (Actin, cytoplasmic 1, Accession No. P60709), immunoglobulin gamma-3 chain C region (Ig gamma-3 chain C region, Accession No. P01860) ), Hemoglobin subunit alpha (Accession No. P69905), Mitochondrial malate dehydrogenase (Malate dehydrogenase, mitochondrial, Accession No. P40926), S10AB (Protein S100-A11, Accession No. P31949), Annexin A1 (Annexin A1, Accession No. P04083), Annexin A3 (Annexin A3, Accession No. P 12429), mitochondrial 10 kD heat shock protein (mitochondrial, Accession No. P61604), serum albumin (Serum albumin, Accession No. P02768), ACTA (Actin, aortic smooth muscle, Accession No. P62736), ERH ( Enhancer of rudimentary homolog, Accession No. Guanine nucleotide binding protein G (I) / G (S) / G (O) subunit gamma-12 (Guanine nucleotide-binding protein G (I) / G (S) / G (O) subunit gamma-12) , Accession No. Q9UBI6), Protein-glutamine gamma-glutamyltransferase 2 (Accession No. P21980), Ras-related C3 botulinum toxin substrate 2 (Ras-related C3 botulinum toxin substrate 1 , Accession No. P63000), mitochondrial ATP synthase subunit alpha (ATP synthase subunit alpha, mitochondrial, Accession No. P25705), prohibitin (Prohibitin, Accession No. P35232), amine oxidase [flavin-containing] A (Amine oxidase [flavin-containing] A, Accession No. P21397), TINAL (Tubulointerstitial nephritis antigen-like, Accession No. Q9GZM7), Apolipoprotein A-1 (Apolipoprotein AI, Accession No. P02647), mitochondria 60 kD heat shock protein (60 kDa heat shock protein, mitochondrial, Accession No. P10809), superoxide Dismutase [Cu-Zn] (Superoxide dismutase [Cu-Zn], Accession No. P00441), NADH-cytochrome b5 reductase 1 (NADH-cytochrome b5 reductase 1, Accession No. Q9UHQ9), neuron specific calcium Binding protein hippocalcin, Accession No. P84074), S10A6 (Protein S100-A6, Accession No. P06703), mitochondrial ATP synthase subunit delta (ATP synthase subunit delta, mitochondrial, Accession No. P30049), Carbonic anhydrase 1, Accession No. P00915) , Clusterin (Accession No. P10909), Myosin regulatory light chain MRLC2 (Accession No. O14950), Annexin A6 (Annexin A6, Accession No. P08133), transmembrane glycoprotein NMB (Transmembrane) glycoprotein NMB, Accession No. Q14956), Collagen alpha-3 (VI) chain, Accession No. P12111), Galectin-1 (Galectin-1, Accession No. P09382), Fibrinogen Beta Fibrinogen beta chain, Accession No. P02675, Alpha-2-HS-glycoprotein, Accession No. P02765, Cell division control protein 42 homolog, Accession No P60953), Serotransferrin (Accession No. P02787), Annex A4 (Annexin A4, Accession No. P09525), S10A A (Protein S100-A10, Accession No. P60903), Synaptic glycoprotein SC2 (Accession No. Q9NZ01), guanine nucleotide conjugate protein G (I) / G (S) / G (O) subunit Gamma-5 (Guanine nucleotide-binding protein G (I) / G (S) / G (O) subunit gamma-5, Accession No. P63218), Talin-1 (Accession No. Q9Y490), Tripeptidyl Peptidase 1 (Tripeptidyl-peptidase 1, Accession No. O14773), Mitochondria 3-ketoacyl-CoA Thiolase (3-ketoacyl-CoA thiolase, mitochondrial, Accession No. P42765), mitochondrial glutamate dehydrogenase 1 (mitochondrial, Accession No. P00367), nidogen-2 (Nidogen-2, Accession No. Q14112), alpha-2-HS-sugar Protein (Alpha-2-HS-glycoprotein, Accession No. P02765), Peptidyl-prolyl cis-trans isomerase B (Accession No. P23284), mitochondrial ATP synthase subunit Beta (ATP synthase subunit beta, mitochondrial, Accession No. P06576), NADH dehydrogenase [ubiquinone] 1 alpha subcomplexone 1 alpha subcomplex subunit 2, Accession No. O43678, clathrin heavy chain 1 (Clathrin heavy chain 1, Accession No. Q00610), basement membrane specific heparin Basement membrane-specific heparan sulfate proteoglycan core protein, Accession No. P98160, K0146 (Uncharacterized protein KIAA0146, Accession No. Q14159), Apolipoprotein (a) (Apolipoprotein (a), Accession No. P08519), and mitochondrial thioredoxin (Thioredoxin, mitochondrial, Accession No. Q99757). The method of claim 3, The protein is hemoglobin subunit beta (Accession No. P6887), hemoglobin subunit gamma-1, Accession No. P69891), H3L (H3-Histone H3-like, Accession No. Q6NXT2) ), Chorionic somatomammotropin hormone (Accession No. P01243), Vitronectin (Vitronectin, Accession No. P04004), Fibronectin (Fibronectin, Accession No. P02751), Annexin A5 (Annexin A5, Accession) No. P08758), and at least one member selected from the group consisting of Annexin A2 (Annexin A2, Accession No. P07355). The method of claim 3, The peptide is a placental peptide mixture is one or more selected from the group consisting of peptides consisting of the amino acid sequence of SEQ ID NO: 1 to 129. The method of claim 5, The peptide is a placental peptide mixture is one or more selected from the group consisting of peptides consisting of the amino acid sequence of SEQ ID NO: 1 to 34. Claims 1 to 6, comprising a peptide mixture according to any one of claims as an active ingredient, a composition for inducing bone differentiation of stem cells. A composition for preventing or treating bone diseases comprising the peptide mixture according to any one of claims 1 to 6 as an active ingredient. The method of claim 8, The bone disease is a composition for preventing or treating bone diseases selected from the group consisting of osteoporosis, bone dysplasia, fracture, osteomalacia, Paget's disease and periodontal disease. A composition for bone regeneration comprising the peptide mixture according to any one of claims 1 to 6 as an active ingredient. Hydrolyzing the placenta with an acid solution of pH 2-3 at 95-105 ° C. for 1-4 hours, The acid is at least one selected from the group consisting of acetic acid, trifluoroacetic acid (TFA), and formic acid, Process for the preparation of placental peptide mixture. The method of claim 11, Further comprising the step of taking the supernatant by centrifuging the obtained hydrolyzate Process for the preparation of placental peptide mixture. 13. The method according to claim 11 or 12, Further comprising the step of lyophilizing the obtained hydrolyzate or supernatant to remove the acid Process for the preparation of placental peptide mixture. Separating the mesenchymal stem cells from the bone marrow, and Incubating the isolated mesenchymal stem cells with the peptide mixture according to any one of claims 1 to 6. Induction of bone differentiation of stem cells comprising a.

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