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Our Ingredients

Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40

Salmon extract DNA

Tranexamic acid

High-purity 3MDa hyaluronic acid, Trehalose & Glutathion

ABOUT BOTULINUM

TEST RESULTS

SAFETY TESTS

REGISRTAION STATUS

Botulinum

The name ‘botulinum’ comes from the Latin word ‘Botulus’, which means black sausage.’Botulinum toxin’ is a neurotoxin protein produced by the bacterium ‘Clostridium botulinum’ that inhibits the secretion of neurotransmitters. Botulinum toxin’ medicine injection is used to treat neuromuscular disorders using temporary paralysis. It is also widely used commercially for medicines, cosmetics, and research.

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Clostridium Botulinum Bacteria

Botulinum

The name ‘botulinum’ comes from the Latin word ‘Botulus’, which means black sausage.’Botulinum toxin’ is a neurotoxin protein produced by the bacterium ‘Clostridium botulinum’ that inhibits the secretion of neurotransmitters. Botulinum toxin’ medicine injection is used to treat neuromuscular disorders using temporary paralysis. It is also widely used commercially for medicines, cosmetics, and research.

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Clostridium Botulinum Bacteria
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DermoToxin

In recent years, ‘DermoToxin’, which injects ‘Botulinum toxin’ medicine directly into the dermal layer of the skin rather than the muscle layer, has become a general procedure for skin improvement in a dermatology hospital.

‘Dermotoxin’ treatment is known to have a effects not only to improve natural facial wrinkles but also to hydration, pore improvement, bright skin tone, elasticity and lifting compared to general intramuscular injection. It is known as a disadvantage that the pain from injection procedure due to the large number on sites and relatively short duration of efficacy.

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DermooToxin

In recent years, ‘DermooToxin’, which injects ‘Botulinum toxin’ medicine directly into the dermal layer of the skin rather than the muscle layer, has become a general procedure for skin improvement in a dermatology hospital.

‘Dermotoxin’ treatment is known to have a effects not only to improve natural facial wrinkles but also to hydration, pore improvement, bright skin tone, elasticity and lifting compared to general intramuscular injection. It is known as a disadvantage that the pain from injection procedure due to the large number on sites and relatively short duration of efficacy.

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OUR INGREDIENT

Structure of ‘Methionyl r-Clostridium

Botulinum Polypeptide-1 Hexapeptide-40′

‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’ is developed as recombination of peptide called “MTD” (Macro-molecule Transmission Domain) that has function of skin and target cell permeation and, active protein of botulinum toxin called ‘Light Chain’.  ‘MTD’ applied to our ingredient is originated and developed from botulinum toxin ‘Heavy Chain’, ,which performing a cell-penatration function of botulinum toxin. 

OUR INGREDIENT

Structure of ‘Methionyl r-Clostridium

Botulinum Polypeptide-1 Hexapeptide-40′

‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’ is developed as recombination of peptide called “MTD” (Macro-molecule Transmission Domain) that has function of skin and target cell permeation and, active protein of botulinum toxin called ‘Light Chain’.  ‘MTD’ applied to our ingredient is originated and developed from botulinum toxin ‘Heavy Chain’, ,which performing a cell-penatration function of botulinum toxin. 

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Vector        pET21b

Insert         MTD       ~20 amino acid                                                                                                                   Name : Clostridium botulinum neurotoxin type A light chain

                   Lc            Amino acid: 447 amino acid                                                                                                       Sequence : Clostridium botulinum type A Hall Lc

                  Tag            Hexa-histidine

ingredient2
Vector        pET21b

Insert         MTD       ~20 amino acid                                                                                                                   Name : Clostridium botulinum neurotoxin type A light chain

                   Lc            Amino acid: 447 amino acid                                                                                                       Sequence : Clostridium botulinum type A Hall Lc

                  Tag            Hexa-histidine

ingredient2

COMPARISON IF BOTULINUM INGREDIENTS

Toxin Complex
(Medical Botox Injection)

 

Pure Toxin
(Medical Botox Injection)

 

Our ingredient 
(BPMed_BoLCA_Protine)

 

Composition

Composition

Composition

Heavy chain : Nerve cell penetration
Light chain : Botulinum Efficacy Part
Hemagglutinin
Non-toxin Non-Hemagglutinin

Heavy chain : Nerve cell penetration
Light chain : Botulinum Efficacy Part

Light Chain + MTD
Botulinum Efficacy Part
Marco-molecule Transmission Domain
(Skin & Nerve cell penetration)
= Recombination of the Protein

Commercialization

Commercialization

Commercialization

1980

1995

2014

Example

Example

Example

BOTOX (Allergan, US)
MEDITOXIN (Meditox, Korea)
Not permitted to use in Cosmetic Product

XEOMIN (Merz, Germany)
Not permitted to use in Cosmetic Produc

BLOOM Planet LTD 
The First Botulinum Ingredient on ICID

Molecular weight

Molecular weight

Molecular weight

900KDa

150KDa

50KDa

Skin And Cell Penetration Technology of MTD

Platform technology to improve transdermal delivery of 

‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’

1st Action 

 Improved penetration of functional materials into stratum corneum and other skin layers by MTD.

2nd Action   

Maximized efficacy through the delivery of  ‘Methionyl r-Clostridium Botulinum Polypeptide-1  Hexapeptide-40’ into specific targets.

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Skin And Cell Penetration Technology of MTD

Platform technology to improve transdermal delivery of 

‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’

1st Action 

 Improved penetration of functional materials into stratum corneum and other skin layers by MTD.

2nd Action   

Maximized efficacy through the delivery of  ‘Methionyl r-Clostridium Botulinum Polypeptide-1  Hexapeptide-40’ into specific targets.

Capture65.PNG
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Modality of Intracellular delivery of MTD in ‘Methionyl

r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40′

Permeate in to cell by MTD technology shows very high Permeability and significantly less cell damage then nano liposome or common peptide ingredients(PTD).

Modality of Intracellular delivery of MTD in ‘Methionyl

r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40′

Permeate in to cell by MTD technology shows very high Permeability and significantly less cell damage then nano liposome or common peptide ingredients(PTD).

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MECHANISM ON NERVE CELL

SNARE Complex Exocitosis Acetylcholine Diffusion 

Binds to the Receptors on the Muscle

Approaching to the Cell

Moves to the SNAP25 

Methionyl r-Clostridium Botulinum 

Polypeptide-1 Hexapeptide-40

Direct Cell Membrane Translocation

Cleaves SNAP25 by Light Chain Part

TEST RESULTS

SNAP25 Cleavage Diagram

Recombinant GST-SNAP25-EGFP is purified in order to review activation of ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’ protein. Since wild type Botulinum Toxin Light Chain cleaves an C-terminal part of SNAP25, GST & EGFP are recombined with 25kDa size on each N-terminal and C-terminal, and purified in order to authentically confirm cleavage form. 75kDa GST-SNAP25-EGFP is cleaved into 50kDa and 25kDa proteins by ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’.

SNAP25 Cleavage
Size alteration after GST-SNAP25-EGFP cleavage
in-vitro SNAP25 cleavage assay
Buffer condition: 1mM DTT, 1mM HEPES, 1mM NaCl, 2uM ZnCl₂
Reaction : 37℃ 3hrs
SDS-PAGE loading condition
– 12% SDS-PAGE
– volt : 120V
in vitro SNAP25 Cleavage Assay

React GST-SNAP25-EGFR protein with various dose of  ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’ in vitro to see if GST-SNAP25-EGFP is cleaved by  ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’. As a result, GST-SNAP25-EGFP protein is cleaved into GST-SNAP25(50kDa) and EGFP(25kDa) depend on dose of  ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’.

SNAP25 Cleavage Diagram
Permeation of Keratinocytes by ‘Methionyl r-Clostridium
Botulinum Polypeptide-1 Hexapeptide-40’
Permeation of keratinocytes

Cell treatment on Keratinocytes cell with FITC conjugated ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’ protein. After 1~6 hours, protein can be seen inside the cell. This result shows that ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’ can penetrate skin.


* Treatment condition
– HaCaT cell
– Peptide : 5Ξm

Vehicle
LC
BPMed_BoLCA
‘Methionyl r-Clostridium Botulinum Polypeptide-1
Hexapeptide-40′ cell penetrate test
Potential in human neuronal cell
Cell treatment on differentiated SiMa cell (Human neuroblastoma) with FITC conjugated ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’ protein. After 3 hours, protein can be seen inside the cell. This result shows that ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’ can be delevered to the human nerve cell, the most important target of Botulinum Protein.
* Treatment condition
– FITC conjugated : 5Ξg
– Time : 3hrs
– Method : confocal
‘Methionyl r-Clostridium Botulinum Polypeptide-1
Hexapeptide-40′ transdermal diffusion test
Transdermal Diffusion
Perform transdermal diffusion test by using Strat-M membrane which is a product from Millipore. Conversion of ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’ amount which is penetrated from 30minutes to 24 hours, into cumulative frequency by using ELISA. Penetrated continuously even after 24 hours

SAFETY TESTS

The following safety tests were performed on the raw material ” Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40 ”.

   – Cell toxicity (in-House Lab.)
   – Bacterial Reverse Mutation Assay test (GLP Lab.)
   – Chromosomal test (GLP Lab.)

The following additional tests are conducted on the safety of ‘Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40’ and animal testing of this ingredient is never carried out.

   – Skin Irritation using EPISKIN
   – Eye Irritation using EpiOcular test​
   – Skin Sensitization : Local Lymph node Assay : BrdU-ELISA)​
   – in vitro 3T3 NRU Photoxity Test 

CLINICAL TESTS

Single Human Patch Test
Bolca Anti-Wrinkle Facial Serum
(I.E.C. Korea @ Chonnam National Univ. Hospital)
Clinical Test (I.E.C. Korea)
Bolca Anti-Wrinkle Facial Serum
(I.E.C. Korea)
D0
D28

Effectivenss

Ratio 

Roughness

16/22

72 %

Net Elasticity

22/22

100 %

Nasolabial line

15/22

68 %

After 4 weeks test shows improvement of roughness, elasticity, nasolabial line from 70% of applicant. Different from individuals but the efficacy can be seen normally within 2 weeks

REGISTRAION STATUS

ICID

“Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40 ” was registered on the International Cosmetics Ingredient Dictionary in December 2014. This can be found on page 2096 of the ICID 2016 Vol.2. The INCI name “Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40” is not defined by the applicant company. This is the name assigned by the PCPC who organizes ICID in Washington and global cosmetic companies for classification of the ingredient. ‘Clostridium Botulinum’ designation on INCI name proves that the material actually derived from ‘Botulinum Toxin ‘.

However, the name ‘Clostridium Botulinum’ is not only important. Botulinum toxin light chain’ alone can not can not penetrate nerve cells even it penetrated in to the skin, so it can not be effective. The core technology of MTD which realizes infiltration into the skin and infiltration of nerve cells has been applied, and botulinum-derived ingredient that we have dreamed of has been born. The ingredient has name ‘Clostridium Botulinum’ can be developed but the technology and efficacy can not be imitated.

REGISTRAION STATUS

ICID

“Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40 ” was registered on the International Cosmetics Ingredient Dictionary in December 2014. This can be found on page 2096 of the ICID 2016 Vol.2. The INCI name “Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40” is not defined by the applicant company. This is the name assigned by the PCPC who organizes ICID in Washington and global cosmetic companies for classification of the ingredient. ‘Clostridium Botulinum’ designation on INCI name proves that the material actually derived from ‘Botulinum Toxin ‘.

However, the name ‘Clostridium Botulinum’ is not only important. Botulinum toxin light chain’ alone can not can not penetrate nerve cells even it penetrated in to the skin, so it can not be effective. The core technology of MTD which realizes infiltration into the skin and infiltration of nerve cells has been applied, and botulinum-derived ingredient that we have dreamed of has been born. The ingredient has name ‘Clostridium Botulinum’ can be developed but the technology and efficacy can not be imitated.

PCT/KR2015/005434
PATENT

Novel cell penetrating peptide, conjugate thereof with botulinum toxin, and use thereof Patent pending technology patent of ” Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40 ” is currently being filed in eight major countries in the world. This technology patent was developed through joint research between ATGC Co., Ltd., which possesses botulinum toxin technology,  and Procel Therapeutics Co., Ltd., which possesses skin and target cell penetration technology.
BPMed Cosmetic Co., Ltd. owns the exclusive right to use the patent and the exclusive right to use the material.

  • Completed patent registration in Korea (KR.10-1882461)
  • Completed patent registration in Japan (JP.6243577)
  • Completed patent registration in Russia (RUS.2670135)
  • Completed patent registration in USA (US.10300118B2)
  • Completed patent registration in Canada (CA.2,949,653)
  • Completed patent registration in China(CN.106459155B)
  • Registration in European (EP.3156412)
PATENT

Novel cell penetrating peptide, conjugate thereof with botulinum toxin, and use thereof Patent pending technology patent of ” Methionyl r-Clostridium Botulinum Polypeptide-1 Hexapeptide-40 ” is currently being filed in eight major countries in the world. This technology patent was developed through joint research between ATGC Co., Ltd., which possesses botulinum toxin technology,  and Procel Therapeutics Co., Ltd., which possesses skin and target cell penetration technology.
BPMed Cosmetic Co., Ltd. owns the exclusive right to use the patent and the exclusive right to use the material.

  • Completed patent registration in Korea (KR.10-1882461)
  • Completed patent registration in Japan (JP.6243577)
  • Completed patent registration in Russia (RUS.2670135)
  • Completed patent registration in USA (US.10300118B2)
  • Completed patent registration in Canada (CA.2,949,653)
  • Completed patent registration in China(CN.106459155B)
  • Registration in European (EP.3156412)
Patent Registration Competion USA
Patent Registration Competion Japan
Patent Registration Competion Korea
Patent Registration Competion Russia
Patent Registration Competion China
Patent Registration Competion Canada

2. Salmon extract DNA

BENEFITS AND MECHANISMS:

  1. Improving microcirculation via process called angiogenesis. PDRN causes increased expression of a growth factor called Vascular Endothelial Growth Factor (VEGF) needed for the growth of blood vessels. Blood vessels are the highway for oxygen and nutrients for cells to grow and repair.
  2. Anti-inflammatory effects on tissues. Inflammation generates free radicals which damages the cells. If these damaged cells are unable to repair themselves, the cells will be removed via apoptosis, our body’s natural repair system. Through multiple mechanisms and cytokines, PDRN has been shown to have an anti-inflammatory effect and even reduce scar formation.
  3. Improves skin texture and elasticity. Collagen synthesis is enhanced by fibroblast activation. This also results in treatment of fine lines in the skin.
  4. Tissue repair and wound healing. PDRN salvages DNA and RNA fragments from damaged cells to incorporate them into new DNA for normal cell proliferation and recovery .
  5. Protection from UV damage- UV rays from the sun cause damage to our DNA and this accelerates signs of aging. PDRN has been shown to enhance DNA repair and clearance of toxic by-products of UV-damaged cells .

WHY SALMON IS SAFE?

The PDRN/DNA is derived from Salmon germ cells (that’s science speak for Salmon sperm cells).
The PDRN/DNA is then subjected to a very rigorous purification process that removes any antigens or proteins that might cause immune or biocompatibility reactions. Salmon DNA is very similar to human DNA. As alluded to above, the rigorous purification that the salmon cells are subjected to removes any proteins that may cause immune reactions.

3. Tranexamic acid

The basic chemical structure is trans-4 aminomethylcyclohexanecarboxylic acid (trans-AMCHA). It inhibits the plasminogen activator by reversibly blocking the lysine binding sites on both plasminogen and plasmin, a molecule responsible for degradation of fibrin. Plasmin is also known to play a role in activation of complement, neutrophils and monocytes and its inhibition thus may also have an anti-inflammatory effect.

Studies have found that it can inhibit UV- induced melanin synthesis by “blocking the interaction between keratinocytes [aka skin cells] and melanocytes [aka, melanin-producing cells], 

4. High-purity 3MDa hyaluronic acid, Trehalose & Glutathion

3D HA Medical Grade
An innovative concept obtained through a unique process that enriches products with Hyaluronic Acid molecules with 3 different ranges of molecular weight. Due to their nature, they penetrate different layers of the skin, giving birth to a 3D uniform structure in the skin: shorter chains penetrate deeper than longer ones, building up a homogeneous and effective system to restore the inflamed or aged skins.

â€Ē Restoration and optimal hydration.
â€Ē Aging prevention.
â€Ē Healing properties.
â€Ē Natural barrier for the skin.
â€Ē Preventing from aggressions and preserving the right nutrients.
â€Ē Immediately visible effects.
â€Ē Enhancement of skin brightness.
â€Ē Improvement in skin texture.
â€Ē Improvement in skin elasticity and tone.

Trehalose, Arginine and Glutathion
Enhanced moisturizing by superior water adsorption capacity Enhanced skin elasticity through fibroblast cell activation and antioxidant function through increasing the stability of vitamin C and E

3D HA Medical Grade
An innovative concept obtained through a unique process that enriches products with Hyaluronic Acid molecules with 3 different ranges of molecular weight. Due to their nature, they penetrate different layers of the skin, giving birth to a 3D uniform structure in the skin: shorter chains penetrate deeper than longer ones, building up a homogeneous and effective system to restore the inflamed or aged skins.

â€Ē Restoration and optimal hydration.
â€Ē Aging prevention.
â€Ē Healing properties.
â€Ē Natural barrier for the skin.
â€Ē Preventing from aggressions and preserving the right nutrients.
â€Ē Immediately visible effects.
â€Ē Enhancement of skin brightness.
â€Ē Improvement in skin texture.
â€Ē Improvement in skin elasticity and tone.

Trehalose, Arginine and Glutathion
Enhanced moisturizing by superior water adsorption capacity Enhanced skin elasticity through fibroblast cell activation and antioxidant function through increasing the stability of vitamin C and E

Hair Stenz Cells

February 25, 2020

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