US20210024594A1 - Therapeutic Agent for Psoriasis - Google Patents

Therapeutic Agent for Psoriasis Download PDF

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Publication number
US20210024594A1
US20210024594A1 US16/967,919 US201916967919A US2021024594A1 US 20210024594 A1 US20210024594 A1 US 20210024594A1 US 201916967919 A US201916967919 A US 201916967919A US 2021024594 A1 US2021024594 A1 US 2021024594A1
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Prior art keywords
psoriasis
amino acid
acid sequence
peptide
day
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US16/967,919
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English (en)
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Katsuto Tamai
Takashi SHIMBO
Takehiko Yamazaki
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StemRIM Inc
University of Osaka NUC
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Osaka University NUC
StemRIM Inc
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Assigned to StemRIM Inc. reassignment StemRIM Inc. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: YAMAZAKI, TAKEHIKO
Assigned to OSAKA UNIVERSITY reassignment OSAKA UNIVERSITY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SHIMBO, Takashi, TAMAI, KATSUTO
Publication of US20210024594A1 publication Critical patent/US20210024594A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • compositions for the prevention and/or treatment of psoriasis which comprise a fragment peptide of the high mobility group box 1 (HMGB1) protein.
  • Psoriasis is a chronic skin disease characterized by inflammation of the skin and abnormal proliferation of keratinocytes. Although the cause of psoriasis is not yet fully elucidated, the disease is thought to develop by genetic factors plus various external factors (infectious diseases, stress, drugs, etc.). In recent years, it has been shown that abnormalities in immune function are involved.
  • corticosteroids for the treatment of psoriasis, corticosteroids, vitamin D3 derivatives, immunosuppressants (such as cyclosporin), vitamin A derivatives (retinoids), biological preparations (e.g., anti-TNF- ⁇ antibodies, anti-IL-17A antibodies, and anti-IL-17 receptor A antibodies), and such have been used; however, there are cases where sufficient effect cannot be obtained.
  • immunosuppressants such as cyclosporin
  • vitamin A derivatives retinoids
  • biological preparations e.g., anti-TNF- ⁇ antibodies, anti-IL-17A antibodies, and anti-IL-17 receptor A antibodies
  • An objective of the present application is to provide novel pharmaceuticals that are effective in the treatment of psoriasis.
  • an HMGB1 fragment peptide having a specific amino acid sequence exhibits an effect of suppressing erythema, scaling (desquamation), and thickening (infiltration) of the skin in an animal model of psoriasis. Accordingly, the present application provides pharmaceutical compositions for the prevention and/or treatment of psoriasis, which comprise the specific HMGB1 fragment peptide.
  • a pharmaceutical composition for the prevention and/or treatment of psoriasis comprising a substance described in any of the following (a) to (c) (herein below referred to as substance A):
  • a method of preventing and/or treating psoriasis comprising administering an effective amount of substance A to a subject.
  • a method of suppressing a skin symptom selected from the group consisting of erythema, thickening, and scaling or desquamation in a patient with psoriasis comprising administering an effective amount of substance A to the patient.
  • Substance A for use in the prevention and/or treatment of psoriasis.
  • Substance A for use in the suppression of a skin symptom selected from the group consisting of erythema, thickening, and scaling or desquamation in a patient with psoriasis.
  • substance A in the manufacture of a medicament for the prevention and/or treatment of psoriasis.
  • substance A in the manufacture of a medicament for the suppression of a skin symptom selected from the group consisting of erythema, thickening, and scaling or desquamation in a patient with psoriasis.
  • FIG. 1 presents photographs of the back of mice used as a criterion for scoring erythema.
  • the numbers (0-4) above the photographs represent the scores corresponding to the degree of erythema (no symptoms: 0, mild: 1, moderate: 2, severe: 3, and extremely severe: 4).
  • FIG. 2 presents photographs of the back of mice used as a criterion for scoring scaling.
  • the numbers (0-4) above the photographs represent the scores corresponding to the degree of scaling (no symptoms: 0, mild: 1, moderate: 2, severe: 3, and extremely severe: 4).
  • FIG. 3 is a graph showing the change in the PASI score after the start of imiquimod application.
  • the PASI score on the 5th day from the start of imiquimod application (Day 5) was significantly different between the control group (see “IMQ/saline”) and the HMGB1 peptide (1-44) administration group (see “IMQ/1-44”) (*p ⁇ 0.05).
  • the PASI score is shown as a missing value because the value of measuring skin thickness could not be obtained due to a problem with the measuring instrument.
  • FIG. 4 presents graphs showing the changes in the erythema, scaling, and thickening scores after the start of imiquimod application.
  • the thickening score is shown as a missing value because the value of measuring skin thickness could not be obtained due to a problem with the measuring instrument.
  • FIG. 5 presents photographs of the back of the mice on the 5th day from the start of imiquimod application.
  • FIG. 6 presents graphs showing the expression levels of the inflammatory cytokines in the skin on the 5th day from the start of imiquimod application.
  • FIG. 7 is a graph showing the change in the PASI score after the start of imiquimod application.
  • FIG. 8 presents graphs showing the expression levels of the inflammatory cytokines in the skin on the 5th day from the start of imiquimod application.
  • compositions for the prevention and/or treatment of psoriasis which comprise an HMGB1 fragment peptide comprising the amino acid sequence described in SEQ ID NO: 1.
  • psoriasis includes, but is not limited to, plaque psoriasis, psoriasis arthropica (psoriatic arthritis), guttate psoriasis, psoriatic erythroderma, and generalized pustular psoriasis.
  • the psoriasis of the present application is plaque psoriasis.
  • plaque psoriasis The main symptoms of plaque psoriasis include “erythema”, where the skin becomes red, “thickening (also referred to as infiltration)”, where the skin is raised, “scaling”, where excessively grown keratin is piled up like scabs, and “desquamation”, where the scaling comes off.
  • pharmaceutical composition is used interchangeably with “medicament”, “drug”, or “pharmacological composition”.
  • the pharmaceutical compositions of the present application are used for suppressing a skin symptom selected from the group consisting of erythema, thickening (infiltration), and scaling or desquamation in patients with psoriasis.
  • a skin symptom selected from the group consisting of erythema, thickening (infiltration), and scaling or desquamation in patients with psoriasis.
  • the pharmaceutical compositions of the present application can be used to suppress these skin symptoms in patients with plaque psoriasis.
  • an HMGB1 fragment peptide comprising the amino acid sequence described in SEQ ID NO: 1 refers to a peptide consisting of a portion of the HMGB1 protein and comprising the amino acid sequence described in SEQ ID NO: 1.
  • Such a peptide can be obtained as genetic recombinants by incorporating DNA encoding the peptide into an appropriate expression system or can be synthesized artificially.
  • examples of the HMGB1 protein include, but are not limited to, proteins comprising the amino acid sequence described in SEQ ID NO: 2 and proteins encoded by DNA comprising the nucleotide sequence described in SEQ ID NO: 3.
  • peptides that comprise an amino acid sequence with one or more amino acid residues modified (substituted, deleted, inserted, or added) in the amino acid sequence described in SEQ ID NO: 1 and that are functionally equivalent to an HMGB1 fragment peptide comprising the amino acid sequence described in SEQ ID NO: 1 can be used instead of or in combination with an HMGB1 fragment peptide comprising the amino acid sequence described in SEQ ID NO: 1.
  • peptides include, but are not limited to, peptides of the following i) to iv), and peptides of the following i) to iv) and having the effect of preventing and/or treating psoriasis:
  • a peptide comprising an amino acid sequence in which one or more amino acids (e.g., one to ten, one to nine, one to eight, one to seven, one to six, one to five, one to four, one to three, or one or two) have been substituted, deleted, inserted, or added in the amino acid sequence described in SEQ ID NO: 1;
  • one or more amino acids e.g., one to ten, one to nine, one to eight, one to seven, one to six, one to five, one to four, one to three, or one or two
  • a peptide consisting of an amino acid sequence in which one or more amino acids (e.g., one to ten, one to nine, one to eight, one to seven, one to six, one to five, one to four, one to three, or one or two) have been substituted, deleted, inserted, or added in the amino acid sequence described in SEQ ID NO: 1;
  • one or more amino acids e.g., one to ten, one to nine, one to eight, one to seven, one to six, one to five, one to four, one to three, or one or two
  • a peptide comprising an amino acid sequence having about 80% or more, for example, about 85% or more, about 90% or more, about 91% or more, about 92% or more, about 93% or more, about 94% or more, about 95% or more, about 96% or more, about 97% or more, about 98% or more, or about 99% or more sequence identity with the amino acid sequence described in SEQ ID NO: 1; and
  • a peptide consisting of an amino acid sequence having about 80% or more, for example, about 85% or more, about 90% or more, about 91% or more, about 92% or more, about 93% or more, about 94% or more, about 95% or more, about 96% or more, about 97% or more, about 98% or more, or about 99% or more sequence identity with the amino acid sequence described in SEQ ID NO: 1.
  • an effective amount of the peptide of the present application or a pharmaceutical composition comprising the peptide (hereinafter, referred to as the peptide or such) is administered to a subject for the treatment or prevention of the diseases or symptoms described herein.
  • An effective amount as used herein refers to an amount sufficient for the treatment or prevention of the diseases or symptoms as described herein.
  • Treatment in the present application includes, but is not limited to, alleviation, delay, blockade, improvement, remission, cure, and complete cure.
  • Prevention in the present application includes, but is not limited to, alleviation, delay, and blockade.
  • Subjects in the present application include, without limitation, mammals, birds, fish, and such. Mammals include, but are not limited to, humans and non-human animals, for example, humans, mice, rats, monkeys, pigs, dogs, rabbits, hamsters, guinea pigs, horses, sheep, and whales. In the present application, the term “subject” is used interchangeably with “patient”, “individual”, and “animal”.
  • the site of administration of the peptide or such of the present application there is no limitation on the site of administration of the peptide or such of the present application, and the peptide or such of the present application can exert its effect when administered to any site, such as a site where a symptom of psoriasis appears or a site nearby, a site different from these sites (a site other than these sites), a site separated from a site where a symptom of psoriasis appears, a site distal from a site where a symptom of psoriasis appears, or a site distal and ectopic to a site where a symptom of psoriasis appears.
  • the peptide or such of the present application can also exert its effect when administered to any tissue, such as a tissue different from a tissue where a symptom of psoriasis appears (the skin, joint, and such), a tissue separated from a tissue where a symptom of psoriasis appears, a tissue distal from a tissue where a symptom of psoriasis appears, or a tissue distal and ectopic to a tissue where a symptom of psoriasis appears.
  • tissue such as a tissue different from a tissue where a symptom of psoriasis appears (the skin, joint, and such), a tissue separated from a tissue where a symptom of psoriasis appears, a tissue distal from a tissue where a symptom of psoriasis appears, or a tissue distal and ectopic to a tissue where a symptom of psoriasis appears.
  • Methods of administering the peptide or such of the present application include, but are not limited to, oral administration and parenteral administration.
  • Methods of parenteral administration include, but are not limited to, intravascular (intra-arterial, intravenous, and such), intramuscular, subcutaneous, intradermal, intraperitoneal, nasal, pulmonary, and transdermal administrations.
  • the peptide or such of the present application can also be administered systemically or locally (e.g., subcutaneously, intradermally, or to the skin surface, eyeball or palpebral conjunctiva, nasal mucosa, oral and gastrointestinal mucosa, vaginal and endometrial mucosa, or injured site) by injection administration, for example, intravenous injection, intramuscular injection, intraperitoneal injection, and subcutaneous injection.
  • injection administration for example, intravenous injection, intramuscular injection, intraperitoneal injection, and subcutaneous injection.
  • the administration method can be appropriately selected according to the age and symptoms of a patient.
  • the dose can be selected, for example, from the range of 0.0000001 mg to 1000 mg per kilogram of body weight per administration.
  • the dose can be selected, for example, from the range of 0.00001 to 100000 mg/body for a patient.
  • administering cells secreting the peptide of the present application or gene therapy vectors into which DNA encoding the peptide has been inserted they can be administered so that the amount of the peptide is within the above range.
  • the pharmaceutical compositions in the present application are not limited to these dosages.
  • compositions of the present application can be formulated according to conventional methods (e.g., Remington's Pharmaceutical Science, latest edition, Mark Publishing Company, Easton, U.S.A.), and may contain pharmaceutically acceptable carriers and additives together.
  • pharmaceutically acceptable carriers and additives include, but are not limited to, surfactants, excipients, coloring agents, perfumes, preservatives, stabilizers, buffers, suspending agents, isotonizing agents, binding agents, disintegrants, lubricants, fluidity-promoting agents, and flavoring agents.
  • Other commonly used carriers can also be used as appropriate.
  • Specific examples include, light anhydrous silicic acid, lactose, crystalline cellulose, mannitol, starch, carmellose calcium, carmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylacetal diethylaminoacetate, polyvinylpyrrolidone, gelatin, medium-chain fatty acid triglycerides, polyoxyethylene hydrogenated castor oil 60, white sugar, carboxymethyl cellulose, cornstarch, and inorganic salts.
  • a cream containing 5% imiquimod (Beselna Cream 5%, manufactured by Mochida Pharmaceutical Co., Ltd.) was used.
  • Imiquimod is represented as IMQ in the drawings corresponding to the Examples of this application.
  • a peptide consisting of amino acid residues 1-44 of the human-derived HMGB1 protein (SEQ ID NO: 1) was chemically synthesized by a solid-phase method.
  • the HMGB1 fragment peptide is referred to as the HMGB1 peptide (1-44) and is expressed as an abbreviation “1-44” in the drawings corresponding to the Examples.
  • C57BL/6 mice (7-week-old, female, body weight about 20 g) were prepared, and the hair on the back was removed.
  • the cream containing 5% imiquimod was applied to the dorsal skin of the mice at a dose of 1.25 g/animal/day (62.5 mg/animal/day as imiquimod) once a day for four days.
  • the day when imiquimod was first applied is represented as “the 1st day of the start of imiquimod application (Day 1)”, and the next day onward is represented as “the Xth day from the start of imiquimod application (Day X)”. That is, the last day that imiquimod was applied was the 4th day from the start of imiquimod application (Day 4), and no application was performed on the 5th day from the start of imiquimod application (Day 5).
  • the test substance was administered by injecting an HMGB1 peptide (1-44) solution, which has been adjusted to a concentration of 1 ⁇ g/ ⁇ l with saline as the vehicle, into the vein at a dose of 100 ⁇ l/day (5 mg/kg/day as the peptide dose) for three days from the 1st day of the start of imiquimod application (Day 1).
  • saline was injected into the vein at a dose of 100 ⁇ l/day for three days from the 1st day of the start of imiquimod application.
  • the degree of the symptoms of psoriasis on the dorsal skin of the mice was evaluated by the PASI score for five days from the 1st day of the start of imiquimod application.
  • the PASI score was calculated by quantifying the degree of each of (a) erythema, (b) scaling (desquamation), and (c) thickening (infiltration) of skin using five stages, [no symptoms: 0 points, mild: 1 point, moderate: 2 points, severe: 3 points, and extremely severe: 4 points], and summing up the values of (a), (b), and (c) (minimum 0 points-maximum 12 points).
  • the erythema score was determined by using the photographs of the back of mice shown in FIG. 1 as a criterion for each score and visually comparing them with the condition of the back of the mice to be evaluated.
  • the scaling score was determined by using the photographs of the back of mice shown in FIG. 2 as a criterion for each score and visually comparing them with the condition of the back of the mice to be evaluated.
  • the thickening score was determined as follows: Two measurement sites were determined on the back of the mice, the skin was pinched and its thickness was measured with a caliper, and the average value from the two sites was recorded daily as the skin thickness (mm).
  • Quantification was carried out by giving 0 points when the value of skin thickness of each day relative to the skin thickness on the 1st day of the start of imiquimod application (before application) was less than 1.1, 1 point when the value was 1.1 or more to less than 1.3, 2 points when the value was 1.3 or more to less than 1.5, 3 points when the value was 1.5 or more to less than 1.7, and 4 points when the value was 1.7 or more.
  • FIG. 3 and FIG. 4 respectively show the changes in the PASI score and the scores for each item of erythema, scaling, and thickening up to the 5th day from the start of imiquimod application (see “IMQ/saline” for the control group and “IMQ/1-44” for the HMGB1 peptide (1-44) administration group).
  • the PASI score as well as the erythema, scaling, and thickening scores tended to increase as the days passed in both the control group and the HMGB1 peptide (1-44) administration group.
  • all these scores in the HMGB1 peptide (1-44) administration group were lower than those in the control group.
  • the PASI score in the HMGB1 peptide (1-44) administration group was significantly lower than that in the control group on the 5th day from the start of imiquimod application.
  • the photographs of the back of the mice on the 5th day from the start of imiquimod application are shown in FIG. 5 (see “IMQ/saline” for the control group and “IMQ/1-44” for the HMGB1 peptide (1-44) administration group).
  • FIG. 6 shows the expression levels of the inflammatory cytokines in the skin on the 5th day from the start of imiquimod application (see “IMQ/saline” for the control group and “IMQ/1-44” for the HMGB1 peptide (1-44) administration group).
  • the expression levels of all of IL-6, IL-17F, and IL-22 in the HMGB1 peptide (1-44) administration group were lower than those in the control group.
  • the drugs were prepared and the psoriasis model mice were produced in the same way as Example 1.
  • the peptides were administered in the same way as Example 1 except that the number of mice was changed to six in both the HMGB1 peptide (1-44) administration group and the control group.
  • the degree of the symptoms of psoriasis on the dorsal skin of the mice was evaluated by the PASI score for four days from the 1st day of the start of imiquimod application.
  • the PASI score was calculated in the same manner as Example 1.
  • the dorsal skin of the mice was collected, mRNA was extracted from the skin, and the expression levels of the inflammatory cytokines (IL-1 ⁇ , IL-6, IL-17A, IL-17F, and IL-22), which are known to be involved in the pathogenesis of psoriasis, were analyzed by quantitative PCR.
  • IL-1 ⁇ , IL-6, IL-17A, IL-17F, and IL-22 inflammatory cytokines
  • FIG. 7 shows the change in the PASI score up to the 4th day from the start of imiquimod application (see “IMQ/saline” for the control group and “IMQ/1-44” for the HMGB1 peptide (1-44) administration group). From the 2nd day from the start of imiquimod application, the PASI score increased as the days passed in both the control group and the HMGB1 peptide (1-44) administration group. However, the PASI score in the HMGB1 peptide (1-44) administration group was lower than that in the control group ( FIG. 7 ). The result indicates that the administration of the HMGB1 peptide (1-44) suppressed the skin symptoms in the psoriasis model mice.
  • FIG. 8 shows the expression levels of the inflammatory cytokines in the skin on the 5th day from the start of imiquimod application (see “IMQ/saline” for the control group and “IMQ/1-44” for the HMGB1 peptide (1-44) administration group).
  • the expression levels of all of IL-11 ⁇ , IL-6, IL-17A, IL-17F, and IL-22 in the HMGB1 peptide (1-44) administration group were lower than those in the control group.
  • compositions comprising the peptide of the present application are expected to provide great benefits to patients with psoriasis who cannot obtain a sufficient effect with existing therapeutics.

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US12304933B2 (en) 2018-10-05 2025-05-20 StemRIM Inc. Disease treatment drug based on mesenchymal-stem-cell mobilization
US12421498B2 (en) 2017-12-01 2025-09-23 StemRIM Inc. Ectodermal mesenchymal stem cells and method for producing same
US12428458B2 (en) 2018-02-08 2025-09-30 StemRIM Inc. Therapeutic agent for psoriasis

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5676253B2 (ja) 2008-04-30 2015-02-25 株式会社ジェノミックス 生体内機能的細胞の高効率採取法
JP5865703B2 (ja) 2009-10-28 2016-02-17 株式会社ジェノミックス 骨髄間葉系および／または多能性幹細胞の血中動員による組織再生促進剤
EP3556378B1 (en) 2017-01-27 2025-03-12 StemRIM Inc. Therapeutic agent for cardiomyopathy, old myocardial infarction and chronic heart failure
CA3117107A1 (en) * 2018-10-25 2020-04-30 Osaka University Therapeutic agent for cartilage disorder
EP4147711A4 (en) * 2020-04-20 2024-04-24 Shionogi & Co., Ltd FORMULATION WITH A HMGB1 PARTIAL PEPTIDE
JP2025135028A (ja) * 2022-06-30 2025-09-18 国立大学法人大阪大学 半月板の治療薬

Family Cites Families (105)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5238680B2 (https=) 1972-12-27 1977-09-30
US4732155A (en) 1985-08-27 1988-03-22 The Children's Medical Center Corporation Implantable chemoattractant system
US5133755A (en) 1986-01-28 1992-07-28 Thm Biomedical, Inc. Method and apparatus for diodegradable, osteogenic, bone graft substitute device
US5658894A (en) 1989-04-23 1997-08-19 The Trustees Of The University Of Pennsylvania Compositions for inhibiting restenosis
US5760261A (en) 1990-02-28 1998-06-02 Guttag; Alvin Higher fatty acid derivatives of salicylic acid and salts thereof
US5661127A (en) 1995-05-01 1997-08-26 The Regents Of The University Of California Peptide compositions with growth factor-like activity
JP3018313B2 (ja) 1996-02-23 2000-03-13 雪印乳業株式会社 骨形成促進及び骨吸収防止剤
US6875753B1 (en) 1996-03-14 2005-04-05 The Governors Of The University Of Alberta Methods for cell mobilization using in vivo treatment with hyaluronan (HA)
US20050101564A1 (en) 1996-04-02 2005-05-12 Pilarski Linda M. Methods for cell mobilization using in vivo treatment with hyaluronan (HA)
CN100374159C (zh) 1998-03-17 2008-03-12 中外制药株式会社 一种包含il-6拮抗剂活性成分的炎性肠道疾病的预防或治疗剂
US20040031072A1 (en) 1999-05-06 2004-02-12 La Rosa Thomas J. Soy nucleic acid molecules and other molecules associated with transcription plants and uses thereof for plant improvement
ATE440602T1 (de) 1999-07-28 2009-09-15 Univ Leland Stanford Junior Nicotinrezeptoragonisten in stammzellen und vorlaüferzellinduktion
JP2003517858A (ja) 1999-11-05 2003-06-03 ジェリジーン メディカル コーポレーション 老齢関連の軟組織の欠陥の増強と修復
EP1114862A3 (de) 1999-11-17 2003-08-06 Switch Biotech Aktiengesellschaft Verwendung von Polypeptiden oder diese kodierende Nukleinsäuren zur Diagnose oder Behandlung von Hauterkrankungen sowie ihre Verwendung zur Identifizierung von pharmakologisch aktiven Substanzen
KR20030032922A (ko) 2000-02-24 2003-04-26 싸이트 테라피스 인코포레이티드 세포의 동시 자극 및 농축
JP3421741B2 (ja) 2000-05-18 2003-06-30 筑波大学長 人工骨髄、血球細胞の増殖方法
CN1259973C (zh) 2000-10-25 2006-06-21 中外制药株式会社 含有il－6拮抗剂作为有效成分的牛皮癣的预防或治疗剂
US7754217B2 (en) 2001-03-16 2010-07-13 Bio3 Research Srl HMGB1 protein inhibitors and/or antagonists for the treatment of vascular diseases
DE10121254A1 (de) 2001-04-30 2002-11-07 Switch Biotech Ag MRP8/MRP14 Heterodimers oder seiner Einzelkomponenten alleine oder in Kombination zur Behandlung und/oder Prävention von Hauterkrankungen, Wunden und/oder Wundheilungsstörungen, die durch eine verringerte Menge an MRP8/MRP14 Heterodimeren gekennzeichnet sind
EP1390058A2 (en) 2001-04-30 2004-02-25 Switch Biotech Aktiengesellschaft Mrp8/mrp14 heterodimer, or its individual components in combination, for treating and/or preventing skin diseases, wounds and/or wound-healing disturbances
US7304034B2 (en) 2001-05-15 2007-12-04 The Feinstein Institute For Medical Research Use of HMGB fragments as anti-inflammatory agents
US7220723B2 (en) 2001-05-15 2007-05-22 The Feinstein Institute For Medical Research Inhibitors of the interaction between HMGB polypeptides and toll-like receptor 2 as anti-inflammatory agents
CN100447154C (zh) 2001-05-15 2008-12-31 费因斯坦医学研究学院 利用hmg片段作为抗炎症试剂
ITMI20011986A1 (it) 2001-09-25 2003-03-25 San Raffaele Centro Fond Metodo e composizione per l'attivazione di cellule presentanti l'antigene
CA2467557A1 (en) 2001-11-19 2003-05-30 Kyowa Hakko Kogyo Co., Ltd. Agent which mobilizes multipotential stem cells from tissues to peripheral blood
KR100930139B1 (ko) 2001-12-07 2009-12-07 사이토리 테라퓨틱스, 인크. 처리된 리포애스퍼레이트 세포로 환자를 치료하기 위한시스템 및 방법
FR2833609B1 (fr) 2001-12-19 2004-12-03 Natural Implant Dispositif de prelevement cellulaire ou tissulaire en phase active et utilisations
AU2003228099A1 (en) 2002-07-03 2004-01-23 Centro Cardiologico Monzino S.P.A.-Irccs Use of hmgb1 in the treatment of tissue damage and/or to promote tissue repair
US7553488B2 (en) 2002-07-05 2009-06-30 UNIVERSITé LAVAL Antibodies against S100A8 and S100A9 proteins for modulating inflammatory reactions
WO2004042033A2 (en) 2002-11-01 2004-05-21 The Board Of Trustees Of The Leland Stanford Junior University Circulating stem cells and uses related thereto
GB0226251D0 (en) 2002-11-11 2002-12-18 San Raffaele Centro Fond Acetylated protein
JP2006510619A (ja) 2002-11-20 2006-03-30 クリティカル セラピューティクス，インコーポレイテッド 抗炎症剤としてのｈｍｇｂ断片の使用
US20040156851A1 (en) 2002-11-20 2004-08-12 Critical Therapeutics, Inc. HMGB1 combination therapies
US7470538B2 (en) 2002-12-05 2008-12-30 Case Western Reserve University Cell-based therapies for ischemia
WO2004061456A2 (de) 2003-01-03 2004-07-22 Alcedo Biotech Gmbh Verwendungen von hmgb, hmgn, hmga proteinen
US7772188B2 (en) 2003-01-28 2010-08-10 Ironwood Pharmaceuticals, Inc. Methods and compositions for the treatment of gastrointestinal disorders
WO2004075855A2 (en) 2003-02-26 2004-09-10 Biomed Solutions, Llc Process for in vivo treatment of specific biological targets in bodily fluid
EP1608397B1 (en) 2003-03-28 2008-10-15 Universite Laval S100 protein as neutrophil activator for alleviating neutropenia in cancer treatment
CN1193092C (zh) 2003-03-28 2005-03-16 浙江大学 骨髓间充质干细胞分离和体外扩增培养方法
US20090069227A9 (en) 2003-04-29 2009-03-12 Capogrossi Maurizio C Use of HMGB1 to promote stem cell migration and/or proliferation
AU2004242091C1 (en) 2003-05-07 2009-12-24 La Jolla Institute For Molecular Medicine Administration of hyaluronic acid to enhance the function of transplanted stem cells
US20050014255A1 (en) 2003-05-29 2005-01-20 Board Of Regents, The University Of Texas System Stem cells for clinical and commercial uses
US20060183667A1 (en) 2003-07-11 2006-08-17 Novo Nordisk A/S Stabilised insulin compositions
WO2005025604A2 (en) 2003-09-10 2005-03-24 The General Hospital Corporation Use of hmgb and hmgb fragments to decrease specific immune response
AU2004272607B2 (en) 2003-09-11 2008-11-06 Cornerstone Therapeutics Inc. Monoclonal antibodies against HMGB1
ITRM20040058A1 (it) 2004-02-03 2004-05-03 Marco E Bianchi Inibitori ed antagonisti di hmgb1 in grado di regolare la proliferazione delle cellule muscolari lisce ed endoteliali.
JP2008507505A (ja) 2004-07-20 2008-03-13 プロヴィンシア・イタリアーナ・デッラ・コングレガチォーネ・フィリ・デッリマコラータ・コンセチォーネ−イスティトゥト・デルモパティコ・デッリマコラータ−アイ・アール・シー・シー・エス 創傷治癒のためのｈｍｇｂ１の使用
MX2007001155A (es) 2004-07-29 2007-08-14 Creabilis Therapeutics Spa Uso de inhibidores de k-252a y de quinasa para la prevencion o el tratamiento de patologias asociadas con hmgb1.
JP5622351B2 (ja) 2004-09-03 2014-11-12 クレアビリス・セラピューティクス・エスピーエー プロテアーゼ抵抗性ヒトおよび非ヒトＨＭＧＢ１Ｂｏｘ−Ａ変異体、ならびにそれらの治療／診断への使用
WO2007001422A2 (en) 2004-10-22 2007-01-04 Medimmune, Inc. High affinity antibodies against hmgb1 and methods of use thereof
KR100593397B1 (ko) 2004-10-27 2006-06-28 한국원자력연구소 중배엽 줄기세포 및/또는 ｐ 물질을 함유하는 상처 치유또는 상처 치유 촉진제, 또는 세포 치료제
WO2006047820A1 (en) 2004-11-01 2006-05-11 Newsouth Innovations Pty Limited Use of calgranulin a and b in the promotion and inhibition of mineralized tissue formation
ITRM20050032A1 (it) 2005-01-21 2006-07-22 Marco E Bianchi Inibitori ed antagonisti di hmgb1 in grado di inibire la patogenesi e la progressione della malattia aterosclerotica.
JP5103626B2 (ja) 2005-01-27 2012-12-19 財団法人ヒューマンサイエンス振興財団 間葉系幹細胞を含む細胞シート
ES2345837T3 (es) 2005-03-23 2010-10-04 Biosafe S.A. Sistema integrado para la recogida, el procesamiento y el trasplante de subgrupos de celulas, incluyendo celulas madre adultas, para medicina regenerativa.
KR100775958B1 (ko) 2005-03-30 2007-11-13 김정문 조직재생 기능을 가지는 비활성 폴리펩티드 및 그 제조방법
WO2006114805A2 (en) 2005-04-28 2006-11-02 Fondazione Centro San Raffaele Del Monte Tabor Use of hmgb2 and hmgb3 proteins for medical applications
US20100280493A1 (en) 2005-06-23 2010-11-04 Asha Nayak Methods and Systems for Treating Injured Cardiac Tissue
WO2007011606A2 (en) * 2005-07-18 2007-01-25 Critical Therapeutics, Inc. USE OF HMGBl ANTAGONISTS FOR THE TREATMENT OF INFLAMMATORY SKIN CONDITIONS
WO2007015546A1 (ja) 2005-08-04 2007-02-08 Genomix Co., Ltd 間葉系幹細胞誘導剤及び組織再生促進剤並びに間葉系幹細胞の調製方法
WO2007031100A1 (en) 2005-09-14 2007-03-22 Ostini, Marco Active immunotherapy of life-threatening systemic inflammation
US20090155853A1 (en) 2005-11-18 2009-06-18 Gary Nabel Non-viral gene delivery complex
WO2007076200A2 (en) 2005-11-28 2007-07-05 Medimmune, Inc. Antagonists of hmgb1 and/or rage and methods of use thereof
CA2640087A1 (en) 2006-01-25 2007-08-02 Mount Sinai School Of Medicine Methods and compositions for modulating the mobilization of stem cells
US7829097B2 (en) 2006-02-06 2010-11-09 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Use of HMGB1 for protection against ischemia reperfusion injury
JP4982739B2 (ja) 2006-06-01 2012-07-25 国立大学法人 東京医科歯科大学 ポリグルタミン病の予防・治療剤
JP5244785B2 (ja) 2006-08-11 2013-07-24 小野薬品工業株式会社 ストローマ由来因子−１（ｓｄｆ−１）に対するモノクローナル抗体
CA2663300C (en) 2006-09-15 2014-10-07 Creabilis Therapeutics S.P.A. Polymer conjugates of box-a of hmgb1 and box-a variants of hmgb1
BRPI0718491A2 (pt) 2006-09-15 2013-12-03 Creabilis Therapeutics Spa Conjugados poliméricos do box-a da hmgb1 e variantes do box-a da hmbg1
ES2629086T3 (es) 2006-10-30 2017-08-07 Genomix Co., Ltd. Sustancia farmacéutica para promover la regeneración funcional de tejido dañado
PL2132221T3 (pl) 2007-02-28 2011-04-29 Polyphor Ltd Przyłączone do matrycy peptydomimetyki
CA2629652A1 (en) 2007-04-24 2008-10-24 Yaojiong Wu Compositions for preventing or treating skin defects and methods of use thereof
US8114668B2 (en) 2007-05-14 2012-02-14 Cardiac Pacemakers, Inc. Composition for cold storage of stem cells
JP5814549B2 (ja) 2008-04-30 2015-11-17 株式会社ジェノミックス 損傷組織の機能的再生促進医薬
US8673580B2 (en) 2008-04-30 2014-03-18 Genomix Co., Ltd. Agent for recruitment of bone-marrow-derived pluripotent stem cell into peripheral circulation
JP5676253B2 (ja) 2008-04-30 2015-02-25 株式会社ジェノミックス 生体内機能的細胞の高効率採取法
ES2609006T3 (es) 2009-10-16 2017-04-18 Rutgers, The State University Of New Jersey Procedimeinto de tratamiento de lesión crónica de tejido nervioso usando una estrategia de terapia celular
CA2773356A1 (en) 2009-10-20 2011-04-28 Maine Medical Center Compositions and methods for treating inflammation and fibrosis
JP5865703B2 (ja) 2009-10-28 2016-02-17 株式会社ジェノミックス 骨髄間葉系および／または多能性幹細胞の血中動員による組織再生促進剤
EP2529235B1 (en) 2010-01-29 2019-03-06 Metanomics GmbH Means and methods for diagnosing heart failure in a subject
CN102247392A (zh) 2010-05-21 2011-11-23 中国医学科学院药物研究所 甘草酸治疗扩张型心肌病心脏重构和心功能障碍的用途
JP5950428B2 (ja) 2010-08-05 2016-07-13 日東電工株式会社 線維化組織から正常組織を再生するための組成物
EP2613797B1 (en) 2010-09-09 2015-11-04 University Of Southern California Compositions and methods for the removal of biofilms
PT3358011T (pt) 2011-04-26 2020-04-23 Univ Osaka Péptido para induzir a regeneração de um tecido e a sua utilização
CN102443064A (zh) 2011-11-03 2012-05-09 刘誉 一种基于凝血酶活性的双靶向作用的嵌合多肽及其应用
ES2661500T3 (es) 2012-07-26 2018-04-02 Ospedale San Raffaele S.R.L. Variantes de HMGB1 y sus usos
KR101448800B1 (ko) 2012-10-24 2014-10-13 한양대학교 산학협력단 핵산 전달 복합체
US9688733B2 (en) 2012-10-25 2017-06-27 Genomix Co., Ltd. Method for treating spinal cord injury using HMGB1 fragment
ES2660420T3 (es) 2012-10-25 2018-03-22 Genomix Co., Ltd. Método novedoso para tratar infarto cardiaco utilizando fragmento de HMGB1
AU2014231709A1 (en) 2013-03-15 2015-10-15 Stemcell Technologies Inc. Compositions and methods for obtaining enriched mesenchymal stem cell cultures
GB2514424A (en) 2013-05-25 2014-11-26 Univ Dublin Therapies for Cardiomyopathy
KR101636139B1 (ko) 2013-08-28 2016-07-06 가톨릭대학교 산학협력단 면역조절능이 우수한 sRAGE 과발현 간엽줄기세포 및 이를 포함하는 면역질환의 예방 또는 치료용 세포치료제 조성물
GB201508337D0 (en) 2015-05-15 2015-06-24 Hmgbiotech S R L Novel peptides
US20180161366A1 (en) 2015-05-20 2018-06-14 Biokine Therapeutics Ltd. Methods of obtaining mononuclear blood cells and uses thereof
EP3556378B1 (en) 2017-01-27 2025-03-12 StemRIM Inc. Therapeutic agent for cardiomyopathy, old myocardial infarction and chronic heart failure
US20200038486A1 (en) 2017-04-07 2020-02-06 StemRIM Inc. Therapeutic medicine for fibrous disease
CA3059544A1 (en) 2017-04-25 2018-11-01 Shionogi & Co., Ltd. Peptide for inducing regeneration of tissue, and use thereof
CN111542335A (zh) 2017-12-01 2020-08-14 斯特姆里姆有限公司 炎症性肠病的治疗药
CN111868231B (zh) 2017-12-01 2024-05-31 斯特姆里姆有限公司 外胚层间充质干细胞及其产生方法
US20210024594A1 (en) 2018-02-08 2021-01-28 StemRIM Inc. Therapeutic Agent for Psoriasis
WO2020071520A1 (ja) 2018-10-05 2020-04-09 株式会社ステムリム 間葉系幹細胞の動員活性を有するペプチド
US12304933B2 (en) 2018-10-05 2025-05-20 StemRIM Inc. Disease treatment drug based on mesenchymal-stem-cell mobilization
WO2020158924A1 (ja) 2019-01-31 2020-08-06 国立大学法人大阪大学 母児間免疫寛容を誘導する方法
JP7561348B2 (ja) 2019-07-31 2024-10-04 株式会社ステムリム 間葉系幹細胞の増殖促進または減少抑制のための組成物
IL296982B2 (en) 2020-04-03 2026-04-01 Stemrim Inc Peptide with mesenchymal stem cell migration activity

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11298403B2 (en) 2017-12-01 2022-04-12 StemRIM Inc. Therapeutic agent for inflammatory bowel disease
US12421498B2 (en) 2017-12-01 2025-09-23 StemRIM Inc. Ectodermal mesenchymal stem cells and method for producing same
US12428458B2 (en) 2018-02-08 2025-09-30 StemRIM Inc. Therapeutic agent for psoriasis
US12304933B2 (en) 2018-10-05 2025-05-20 StemRIM Inc. Disease treatment drug based on mesenchymal-stem-cell mobilization

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