WO2012078060A2 - Peptide preparations and peptides with antitumour activity - Google Patents

Peptide preparations and peptides with antitumour activity Download PDF

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Publication number
WO2012078060A2
WO2012078060A2 PCT/PL2011/050049 PL2011050049W WO2012078060A2 WO 2012078060 A2 WO2012078060 A2 WO 2012078060A2 PL 2011050049 W PL2011050049 W PL 2011050049W WO 2012078060 A2 WO2012078060 A2 WO 2012078060A2
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Prior art keywords
nkqvvssseql
lnkqvvssseql
peptides
peptide
vvqidnakl
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WO2012078060A3 (en
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Andrzej Lipkowski
Sergiusz Markowicz
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Instytut Medycyny Doswiadczalnej I Klinicznej Pan
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Instytut Medycyny Doswiadczalnej I Klinicznej Pan
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Priority to US13/992,023 priority Critical patent/US9365633B2/en
Priority to EP11846061.7A priority patent/EP2649089A2/en
Publication of WO2012078060A2 publication Critical patent/WO2012078060A2/en
Publication of WO2012078060A3 publication Critical patent/WO2012078060A3/en
Anticipated expiration legal-status Critical
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/78Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/06Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/08Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Definitions

  • the subject of the present invention are peptide preparations produced as a result of the enzymatic digestion of hair, wool, bristles, animal fur and individual peptides with sequences corresponding to individual components of peptide preparations with antitumour activity for use in the treatment of tumours or oncological prophylaxis as basal components or components of compositions of substances for treating tumours or components of substances used in oncological prophylaxis.
  • Hair (20 g) has been stirred in 0.1 N sodium hydroxide in room temperature for 2 hours. Then hair was filtered off and washed twice with water. Residue has been suspended in water, temperature has been adjusted to 40°C. pH has been adjusted with 10% hydrochloric acid to 1.6. Pepsin (5 mg) has been added and reaction mixture has been stirred at 40°C. The pH has been controlled and adjusted to pH 1.6-1.9 with hydrochloric acid. After 5 hours solid residue has been washed out, and filtrate has been heated to 80°C and after 3 minutes, frozen down to -20°C temperature, and lyophilised. The residual powder has been used for biological assays.
  • the preparation was added at 0.1% concentration into the culture media of tumour cells.
  • a parallel control culture was maintained under identical conditions, but without added preparation. The cultures were maintained over a standardised number of days, under typical conditions. The culture medium was exchanged daily both in the control and experimental cultures. In the experimental culture, the new medium always contained 0.1% of the preparation. After seven days, the number of cells was evaluated in the control and experimental cultures. It turned out that in the case of human melanoma cells, in the control culture the number of cells grew 20-fold over 7 days. In the experimental culture containing 0.1% of the preparation, however, the number of cells remained at the initial level from the outset of the culture.
  • the hair of a 28-year old woman was activated and hydrolysed with pepsin according to the method described in Example I.
  • the portion dissolved as a result of pepsin digestion was lyophilised yielding the preparation for further experiments.
  • the preparation was added at 0.1% concentration into the culture media of tumour cells.
  • a parallel control culture was maintained under identical conditions, but without added preparation.
  • the cultures were maintained over a standardised number of days, under typical conditions.
  • the culture medium was exchanged daily both in the control and experimental cultures. In the experimental culture, the new medium always contained 0.1% of the preparation. After seven days, the number of cells was evaluated in the control and experimental cultures. It turned out that in the case of human melanoma cells, in the control culture the number of cells grew 20-fold over 7 days.
  • Murine bristles were activated and pepsin hydrolysed according to the method described in Example I. The portion dissolved as a result of pepsin digestion was lyophilised yielding the preparation for further experiments.
  • the preparation was added at 0.1% concentration into the culture media of tumour cells.
  • a parallel control culture was maintained under identical conditions, but without added preparation. The cultures were maintained over a standardised number of days, under typical conditions. The culture medium was exchanged daily both in the control and experimental cultures. In the experimental culture, the new medium always contained 0.1% of the preparation. After four days, the number of cells was evaluated in the control and experimental cultures. It turned out that in the case of murine melanoma cells, the addition of the preparation completely inhibited the proliferation of the cells.
  • the precipitate was drained off and washed with the ethyl ether and hexane mixture.
  • the precipitate was dried and purified chromatographically using high-performance preparative chromatography in a gradient of solution A - 0.1% HC1 and solution B-methanol.
  • the resulting pure peptides in the form of hydrochlorides were used in biological tests.
  • the synthetic peptides were examined for their effect on the proliferation of melanoma cells of the line MeW 155.
  • the culture was maintained under standard conditions for 3 days with 4000 cells per well of a 96-well culture plate. After three days, the numbers of cells in the control group increased to 120 000.
  • peptide 91 at a concentration of 0.004 mM decreased cell numbers to 55% of the control, and a 0.02 mM concentration decreased the cells to 35%, whereas 0.1 mM was toxic to MeW 155 cells.
  • Peptide 92 at 0.004 mM decreased the number of tumour cells to 65% of the control, a 0.02 mMol concentration decreased the number of cells to 49%, and a concentration of 0.1 mM was toxic to melanoma cells.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)

Abstract

The subject of the present invention are peptide preparations obtained via the enzymatic digestion of hair, wool, bristles, animal fur and individual peptides with sequences corresponding to individual components of a peptide preparation with antitumour activity, for use in the treatment of tumours or oncological prophylaxis as basal components or components of compositions of substances for treating tumours or components of substances used in oncological prophylaxis.

Description

Peptide preparations and peptides with antitumour activity
The subject of the present invention are peptide preparations produced as a result of the enzymatic digestion of hair, wool, bristles, animal fur and individual peptides with sequences corresponding to individual components of peptide preparations with antitumour activity for use in the treatment of tumours or oncological prophylaxis as basal components or components of compositions of substances for treating tumours or components of substances used in oncological prophylaxis.
It is commonly accepted that hair, fur and bristles constitute natural, physical protection for an organism against mechanical trauma and thermal protection against excessive heat gain/loss. However, despite the great resistance against natural factors that degrade hair, fur or bristles, there exists the possibility of degrading their component proteins by the enzymes of bacteria and fungi that colonize the skin as well as by endogenous enzymes secreted in sweat. It is also observed that animals lick and swallow their fur, which may be partially degraded in the digestive tract, thereby secreting appropriate peptide fragments. Attempts have been made to seek the biological role of peptides constituting hair, fur or bristles. Patent WO 03/064449 describes and claims the use of active peptides from hair or wool in wound healing. Our studies on the conversion of hair or fur or bristles have made it possible to formulate an original method of converting using chemical activation and then pepsin digestion. This method was described and claimed in 1995 by B. Baranowska, A.W. Lipkowski, E. Marczak, I. Makulec, H. Rybak, J. Pastuszak, in "A method of activating keratinous substances by enzymatic hydrolysis ", Polish Patent Nr 179342.
While studying the biological activity of a preparation produced through the enzymatic digestion of hair or wool or animal fur substrates initially activated by alkali activity, it unexpectedly turned out that these preparations exhibit significant antitumour activity against tumours of various aetiology. Further analysis of the peptides constituting the preparations showed that individual component peptides also demonstrate antitumour activity. For this reason, peptide preparations obtained through the appropriate digestion of hair or wool or animal fur may be used as active ingredients in the treatment or prophylaxis of tumours or that constitute components of substances for treatment or prophylaxis.
Examples of activities are given to better illustrate the present invention, the antitumour activities of the resulting preparations or individual component peptides. The scope of the present invention, however, should not be limited solely to the wording of the following examples.
Example 1.
Hair from a 60-year old man was activated and hydrolysed with pepsin according to the method described in A.W. Lipkowski, B. Gajkowska, A. Grabowska, K. Kurzepa, "Keratin-associated protein micromaterials for medical and cosmetic applications.", Polimery, Vol. 54, p. 386-388, 2009.
Hair (20 g) has been stirred in 0.1 N sodium hydroxide in room temperature for 2 hours. Then hair was filtered off and washed twice with water. Residue has been suspended in water, temperature has been adjusted to 40°C. pH has been adjusted with 10% hydrochloric acid to 1.6. Pepsin (5 mg) has been added and reaction mixture has been stirred at 40°C. The pH has been controlled and adjusted to pH 1.6-1.9 with hydrochloric acid. After 5 hours solid residue has been washed out, and filtrate has been heated to 80°C and after 3 minutes, frozen down to -20°C temperature, and lyophilised. The residual powder has been used for biological assays.
The portion dissolved as a result of pepsin digestion was yielding the preparation for further experiments. An analysis of the peptides in the preparation demonstrated the presence of peptides with the sequences given in the table and larger peptide with sequences given in the table.
Table.
Identified short peptide sequences in the
preparation obtained from human hair
Item (amino-acid residues given in the standard
single-letter code)
1 AEIRSDL
2 VVQIDNAKL
3 LVVQIDNAKL
4 NKQVVSSSEQL
5 LNKQVVSSSEQL
6 RQLVESDINGL
7 TESEARYSSQL
8 VVQIDNAKLAADDF
9 NRVLNETRSQYEAL
10 NKQVVSSSEQLQSYQAEIIELR
11 NKQVVSSSEQLQSYQAEIIEL
12 LNKQVVSSSEQLQSYQAEIIEL
13 VVNIDNAKL
14 NKQVVSSSEQL
15 LNKQVVSSSEQL
16 NVEVDTAPTVDL
17 VVNIDNAKLASDDF
18 VVEIDNAKL
19 IQEIDF
20 IDKVRF
21 LEQQNKL
22 ASELNHVQEVL
23 NQQVVSSSEQL
24 NQQVVSSSEQL
25 RQLVESDINGL
26 VVEIDNAKLAADDF
27 IVQIDNAKLAADDF
28 TVIFDTGSSNL
29 GILGPVIKAEVGDTL
30 IQEIDF
31 IDKVRF
32 VVQIDNAKL AEIRSDL
AEIRSDLE
AEIRSDL
VVQIDNAKLA
VVQIDNAKL
NETRSQYEAL
NKQVVSSSEQLQ
NKQVVSSSEQL
LNKQVVSSSEQL
RQLVESDINGL
VVQIDNAKLAADDF
SQVQSLITNVESQL
SQVQSLITNVESQLA
NRVLNETRSQYEALV
NRVLNETRSQYEAL
LNRVLNETRSQYEAL
NKQVVSSSEQLQSYQAEIIEL
NKQVVSSSEQLQSYQAEIIELR
AEIRSDLE
AEIRSDL
LAEIRSDL
VVQIDNAKLA
VVQIDNAKL
NETRSQYEALV
NKQVVSSSEQLQ
NKQVVSSSEQL
LNKQVVSSSEQL
RQLVESDINGL
SQVQRLITNVESQLA
SQVQRLITNVESQL
NQVLNETRSQYEALV
LNQVLNETRSQYEAL
NQVLNETRSQYEAL
NKQVVSSSEQLQSYQAEIIELR
NKQVVSSSEQLQSYQAEIIEL
VVNIDNAKLA
VVNIDNAKL
NETRSQYEALV
NKQVVSSSEQLQ
NKQVVSSSEQL
LNKQVVSSSEQL
VVNIDNAKLASDDF
SQVQSLITNVESQLA
SQVQSLITNVESQL
NQVLNETRSQYEALV
LNQVLNETRSQYEAL
NQVLNETRSQYEAL
LGRVTIAQGGVL 81 PKKTESHHKAKGK
82 IDKVRF
83 LEQQNKL
84 RATAENEF
85 IREYQEVMNSKLGL
86 QNQLEKLG
87 LQNQLEKL
88 QNQLEKL
89 LGKVTIAQGGVLP
90 PKKTESHHKAKGK
91 YRPWGSGSGFG
92 YRPWGSGSGF
93 ERIAGEASRL
94 AKHAVSEGTKAVTKYTSSK
95 DRANNQVGLAPVA
96 FDRANNQVGLAPVA
97 IGGITGPIAKL
98 MEARGPGELC
99 MEARGPGELC
100 IERIPEL
101 TVIFDTGSSNL
102 LIPWVQKPIIF
103 GKEPLGPAL
104 IVNTNVPRASVPDGF
105 MALPVTAL
106 KVGINYQPPTVVPGGDL
107 IDTSRHYLPVKIIL
108 LGRIPSAVGYQPTL
109 VINGNPITIF
110 MKSCGVSL
The preparation was added at 0.1% concentration into the culture media of tumour cells. A parallel control culture was maintained under identical conditions, but without added preparation. The cultures were maintained over a standardised number of days, under typical conditions. The culture medium was exchanged daily both in the control and experimental cultures. In the experimental culture, the new medium always contained 0.1% of the preparation. After seven days, the number of cells was evaluated in the control and experimental cultures. It turned out that in the case of human melanoma cells, in the control culture the number of cells grew 20-fold over 7 days. In the experimental culture containing 0.1% of the preparation, however, the number of cells remained at the initial level from the outset of the culture. In the case of a 4 day culture of urinary bladder tumour cells, a 0.1% addition of preparation in the culture inhibited the growth of the cells to 70% of the control population. In the case of human lymphoma in a 4 day culture, a 0.1% addition of preparation caused a decrease of proliferation to 35% of that of control cells.
Example 2.
The hair of a 28-year old woman was activated and hydrolysed with pepsin according to the method described in Example I. The portion dissolved as a result of pepsin digestion was lyophilised yielding the preparation for further experiments. The preparation was added at 0.1% concentration into the culture media of tumour cells. A parallel control culture was maintained under identical conditions, but without added preparation. The cultures were maintained over a standardised number of days, under typical conditions. The culture medium was exchanged daily both in the control and experimental cultures. In the experimental culture, the new medium always contained 0.1% of the preparation. After seven days, the number of cells was evaluated in the control and experimental cultures. It turned out that in the case of human melanoma cells, in the control culture the number of cells grew 20-fold over 7 days. In the experimental culture containing 0.1% of the preparation, however, the number of cells remained at the initial level from the outset of the culture. In the case of a 4 day culture of urinary bladder tumour cells, a 0.1% addition of preparation in the culture inhibited the growth of the cells to 50% of the control population. In the case of human lymphoma in a 4 day culture, a 0.1% addition of preparation completely inhibited the proliferation of the cells.
Example 3
Murine bristles were activated and pepsin hydrolysed according to the method described in Example I. The portion dissolved as a result of pepsin digestion was lyophilised yielding the preparation for further experiments. The preparation was added at 0.1% concentration into the culture media of tumour cells. A parallel control culture was maintained under identical conditions, but without added preparation. The cultures were maintained over a standardised number of days, under typical conditions. The culture medium was exchanged daily both in the control and experimental cultures. In the experimental culture, the new medium always contained 0.1% of the preparation. After four days, the number of cells was evaluated in the control and experimental cultures. It turned out that in the case of murine melanoma cells, the addition of the preparation completely inhibited the proliferation of the cells.
Example 4
From the list of peptides in the hydrolysate, we arbitrarily selected the peptide sequences 91 (YRPWGSGSGFG) and 92 (YRPWGSGSGF). These peptides were synthesized using the standard Fmoc procedure on a solid phase beginning with appropriate Wanga resin derivatives, Fmoc-Gly-Wang or Fmoc-Phe-Wang. To deprotect the protective group we used 2% piperidine w dimethylformamide (DMF). To attach the subsequent amino-acid we used a 1.5 excess of the appropriate Fmoc-amino-acid in the presence of a 1.5 -fold excess of HATU (0-azobenzotriazol-lyl)-l,l,3,3-tetramethyluronium hexa fluorophosphate)). After synthesizing the peptide with a sequence corresponding to that of peptides 91 or 92, we treated the resin with 99.5% trifluoroacetic acid for 3 minutes. The acid solution was filtered off and rinsed with two small volumes of acid. The combined filtrates were supplemented with a 5-fold volume of an ethyl-ether and hexane mixture (2: 1). The precipitate was drained off and washed with the ethyl ether and hexane mixture. The precipitate was dried and purified chromatographically using high-performance preparative chromatography in a gradient of solution A - 0.1% HC1 and solution B-methanol. The resulting pure peptides in the form of hydrochlorides were used in biological tests. The synthetic peptides were examined for their effect on the proliferation of melanoma cells of the line MeW 155. The culture was maintained under standard conditions for 3 days with 4000 cells per well of a 96-well culture plate. After three days, the numbers of cells in the control group increased to 120 000. It turned out that after 3 days of culture, peptide 91 at a concentration of 0.004 mM decreased cell numbers to 55% of the control, and a 0.02 mM concentration decreased the cells to 35%, whereas 0.1 mM was toxic to MeW 155 cells. Peptide 92 at 0.004 mM decreased the number of tumour cells to 65% of the control, a 0.02 mMol concentration decreased the number of cells to 49%, and a concentration of 0.1 mM was toxic to melanoma cells.

Claims

PK/1420/RW Claims
A peptide preparation with antitumour activity characterised in that it contains an enzymatic hydrolysate of proteins from human hair or bristles or animal fur.
A peptide with antitumour activity selected from a group encompassing the peptides with the following sequences
1 AEIRSDL
2 VVQIDNAKL
3 LVVQIDNAKL
4 NKQVVSSSEQL
5 LNKQVVSSSEQL
6 RQLVESDINGL
7 TESEARYSSQL
8 VVQIDNAKLAADDF
9 NRVLNETRSQYEAL
10 NKQVVSSSEQLQSYQAEIIELR
1 1 NKQVVSSSEQLQSYQAEIIEL
12 LNKQVVSSSEQLQSYQAEIIEL
13 VVNIDNAKL
14 NKQVVSSSEQL
15 LNKQVVSSSEQL
16 NVEVDTAPTVDL
17 VVNIDNAKLASDDF
18 VVEIDNAKL
19 IQEIDF
20 IDKVRF
21 LEQQNKL
22 ASELNHVQEVL
23 NQQVVSSSEQL
24 NQQVVSSSEQL
25 RQLVESDINGL
26 VVEIDNAKLAADDF
27 IVQIDNAKLAADDF
28 TVIFDTGSSNL
29 GILGPVIKAEVGDTL
30 IQEIDF
31 IDKVRF
32 VVQIDNAKL
33 AEIRSDL
34 AEIRSDLE
35 AEIRSDL VVQIDNAKLA
VVQIDNAKL
NETRSQYEAL
NKQVVSSSEQLQ
NKQVVSSSEQL
LNKQVVSSSEQL
RQLVESDINGL
VVQIDNAKLAADDF
SQVQSLITNVESQL
SQVQSLITNVESQLA
NRVLNETRSQYEALV
NRVLNETRSQYEAL
LNRVLNETRSQYEAL
NKQVVSSSEQLQSYQAEIIEL
NKQVVSSSEQLQSYQAEIIELR
AEIRSDLE
AEIRSDL
LAEIRSDL
VVQIDNAKLA
VVQIDNAKL
NETRSQYEALV
NKQVVSSSEQLQ
NKQVVSSSEQL
LNKQVVSSSEQL
RQLVESDINGL
SQVQRLITNVESQLA
SQVQRLITNVESQL
NQVLNETRSQYEALV
LNQVLNETRSQYEAL
NQVLNETRSQYEAL
NKQVVSSSEQLQSYQAEIIELR
NKQVVSSSEQLQSYQAEIIEL
VVNIDNAKLA
VVNIDNAKL
NETRSQYEALV
NKQVVSSSEQLQ
NKQVVSSSEQL
LNKQVVSSSEQL
VVNIDNAKLASDDF
SQVQSLITNVESQLA
SQVQSLITNVESQL
NQVLNETRSQYEALV
LNQVLNETRSQYEAL
NQVLNETRSQYEAL
LGRVTIAQGGVL
PKKTESHHKAKGK
IDKVRF
LEQQNKL 84 RATAENEF
85 IREYQEVMNSKLGL
86 QNQLEKLG
87 LQNQLEKL
88 QNQLEKL
89 LGKVTIAQGGVLP
90 PKKTESHHKAKGK
91 YRPWGSGSGFG
92 YRPWGSGSGF
93 ERIAGEASRL
94 AKHAVSEGTKAVTKYTSSK
95 DRANNQVGLAPVA
96 FDRANNQVGLAPVA
97 IGGITGPIAKL
98 MEARGPGELC
99 MEARGPGELC
100 IERIPEL
101 TVIFDTGSSNL
102 LIPWVQKPIIF
103 GKEPLGPAL
104 IVNTNVPRASVPDGF
105 MALPVTAL
106 KVGINYQPPTVVPGGDL
107 IDTSRHYLPVKIIL
108 LGRIPSAVGYQPTL
109 VINGNPITIF
110 MKSCGVSL
3. A peptide preparation for use in antitumour therapy or prophylaxis characterised in that it contains at least one of the peptides defined in Claim 2.
4. Peptide preparation according to Claim 3, characterised in that it is in the form of a cream, ointment, cosmetic liquid or oral preparation.
5. A peptide preparation according to Claim 3, characterised in that it is a component of an implant or ointment for use in therapy for preventing tumour recurrence.
PCT/PL2011/050049 2010-12-06 2011-12-06 Peptide preparations and peptides with antitumour activity Ceased WO2012078060A2 (en)

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EP11846061.7A EP2649089A2 (en) 2010-12-06 2011-12-06 Peptide preparations and peptides with antitumour activity

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PLPL393153 2010-12-06
PL393153A PL226806B1 (en) 2010-12-06 2010-12-06 Peptide preparations and peptides with anticancer properties

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WO2018012935A1 (en) * 2016-07-14 2018-01-18 경희대학교 산학협력단 Anticancer composition comprising keratin
CN116041427B (en) * 2022-11-18 2023-09-29 中国农业大学 ACE (angiotensin converting enzyme) inhibitory peptide derived from two miscellaneous cereals as well as preparation method and application thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL179342B1 (en) 1995-03-24 2000-08-31 Inst Chemii Przemyslowej Im Pr A method of activating keratin raw materials before enzymatic hydrolysis for cosmetic purposes
WO2003064449A2 (en) 2002-01-28 2003-08-07 Keraplast Technologies, Ltd. Bioactive keratin peptides

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5527773A (en) 1993-08-25 1996-06-18 United States Of America Use of synthetic peptides to disrupt the cytoskeleton
US20040006205A1 (en) * 2001-04-03 2004-01-08 Li Li Therapeutic polypeptides, nucleic acids encoding same, and methods of use
FR2883168B1 (en) * 2005-03-18 2008-01-11 Oreal COSMETIC CARE COMPOSITIONS, REINFORCING AND / OR REPAIRING KERATIN SUBSTRATES COMPRISING KAP POLYPEPTIDES

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL179342B1 (en) 1995-03-24 2000-08-31 Inst Chemii Przemyslowej Im Pr A method of activating keratin raw materials before enzymatic hydrolysis for cosmetic purposes
WO2003064449A2 (en) 2002-01-28 2003-08-07 Keraplast Technologies, Ltd. Bioactive keratin peptides

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
A.W. LIPKOWSKI; B. GAJKOWSKA; A. GRABOWSKA; K. KURZEPA: "Keratin-associated protein micromaterials for medical and cosmetic applications", POLIMERY, vol. 54, 2009, pages 386 - 388, XP009162604

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US20140315824A1 (en) 2014-10-23
US9365633B2 (en) 2016-06-14
EP2649089A2 (en) 2013-10-16
WO2012078060A3 (en) 2013-01-03
PL226806B1 (en) 2017-09-29
PL393153A1 (en) 2012-06-18

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