WO2024097704A1 - Herbal formulation for improvement of skin growth - Google Patents
Herbal formulation for improvement of skin growth Download PDFInfo
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- WO2024097704A1 WO2024097704A1 PCT/US2023/078280 US2023078280W WO2024097704A1 WO 2024097704 A1 WO2024097704 A1 WO 2024097704A1 US 2023078280 W US2023078280 W US 2023078280W WO 2024097704 A1 WO2024097704 A1 WO 2024097704A1
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- Prior art keywords
- composition
- collagen
- marine
- proteoglycans
- skin
- Prior art date
Links
- 230000008470 skin growth Effects 0.000 title description 4
- 239000012674 herbal formulation Substances 0.000 title description 3
- 230000006872 improvement Effects 0.000 title description 3
- 239000000203 mixture Substances 0.000 claims abstract description 34
- 102000008186 Collagen Human genes 0.000 claims abstract description 27
- 108010035532 Collagen Proteins 0.000 claims abstract description 27
- 229920001436 collagen Polymers 0.000 claims abstract description 27
- 102000016611 Proteoglycans Human genes 0.000 claims abstract description 24
- 108010067787 Proteoglycans Proteins 0.000 claims abstract description 24
- 210000004927 skin cell Anatomy 0.000 claims abstract description 23
- 230000010261 cell growth Effects 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 10
- 102000012422 Collagen Type I Human genes 0.000 claims description 9
- 108010022452 Collagen Type I Proteins 0.000 claims description 9
- 230000001737 promoting effect Effects 0.000 claims description 9
- 241000283690 Bos taurus Species 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000006071 cream Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000006210 lotion Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
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- 239000003860 topical agent Substances 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims 6
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 abstract description 4
- 230000012010 growth Effects 0.000 abstract description 3
- 235000015872 dietary supplement Nutrition 0.000 description 20
- 210000003491 skin Anatomy 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- 238000012360 testing method Methods 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 10
- 239000004615 ingredient Substances 0.000 description 7
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- 230000035755 proliferation Effects 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
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- 238000004458 analytical method Methods 0.000 description 3
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- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
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- 102000016942 Elastin Human genes 0.000 description 1
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- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
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- 230000007774 longterm Effects 0.000 description 1
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- 230000008439 repair process Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 230000037377 skin turgor Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
Definitions
- the present invention relates to a nutritional supplement composition
- a nutritional supplement composition comprising marine proteoglycans and collagen that can be administered to a human subject to stimulate skin cell growth.
- the nutritional supplement can be administered in an oral form or as a topical agent.
- the present invention relates to methods of stimulating or promoting skin cell growth in the face or any selected areas of the body. More specifically, the method comprises administering the nutritional supplement composition to a human subject in order to stimulate or promote skin cell growth.
- Skin is composed of the epidermis and the dermis. Below these layers lies the hypodermis, which is not usually classified as a layer of skin.
- the hypodermis is also commonly referred to as subcutaneous fat layer, or subcutaneous tissue.
- the outermost epidermis is made up of stratified squamous epithelium with an underlying basement membrane. It contains no blood vessels and is nourished by diffusion from the dermis.
- the main type of cells which make up the epidermis are keratinocytes, with melanocytes and langerhans cells also present. This layer of skin is responsible for keeping w ater in the body and keeping other harmful chemicals and pathogens out.
- the dermis lies below the epidermis and contains a number of structures including blood vessels, nerves, hair follicles, smooth muscle, glands and lymphatic tissue.
- the dermis (or corium) is typically 3-5 mm thick and is the major component of human skin. It is composed of a network of connective tissue, predominantly collagen fibrils providing support and elastic tissue providing flexibility.
- the main cell types are fibroblasts, adipocytes (fat storage) and macrophages.
- the hypodermis lies below the dermis. Its purpose is to attach the skin to underlying bone and muscle as well as supplying it with blood vessels and nerves. It is made up of loose connective tissue and elastin.
- the main cell types are fibroblasts, macrophages and adipocytes.
- the hypodermis contains 50% body fat. Fat serves as padding and insulation for the body.
- Skin aging occurs as the result of several factors: inherent changes within the skin, effects of gravity, facial muscles acting on the skin (dynamic lines), soft tissue loss or shift and bone loss and loss of tissue elasticity’.
- the skin ages when the epidermis begins to thin, causing the junction with the dermis to flatten. Collagen decreases as a person ages and the bundles of collagen, which gives the skin turgor, become looser and lose strength. When the skin loses elasticity, it is less able to resist stretching. Coupled with gravity, muscle pull and tissue changes, the skin begin to wrinkle. Loss of skin cells and loss of bonds between cells also reduces the barrier function of the skin, w hich can cause the skin's pore size to increase.
- the present invention is a nutritional supplement. It is a novel composition comprising marine proteoglycans and collagen, which stimulates the growth of skin cells.
- a particular embodiment of the present disclosure relates to an oral nutritional supplement that includes the novel composition.
- the composition may be delivered as non-toxic salts thereof, effective complexes thereof, stable chelates thereof, active esters thereof, functional derivatives thereof, and mixtures thereof which are effective to stimulate skin cell growth in the general population.
- a topical nutritional supplement that comprises a mixture of marine proteoglycans and type I collagen.
- the type I collagen is bovine, porcine, or marine collagen.
- Methods of stimulating skin cell growth comprise administering the novel composition to a human subject.
- composition will find applications to stimulate skin cell growth and to promote skin tissue growth, repair the skin, or to rebalance skin proliferation.
- the nutritional supplement includes a composition for promoting skin cell growth comprising marine proteoglycans (obtained from fish cartilage) and collagen in a ratio of 0.1% to 10% marine proteoglycans to 90% to 99.9% collagen.
- the composition comprises marine proteoglycans and collagen in a ration of 0.1% to 99.9%.
- the composition comprises marine proteoglycans and collagen in a ration of 10% to 90%.
- the collagen may be type I collagen and, more specifically, can be bovine collagen.
- a method of promoting skin cell grow th comprises administering the nutritional supplement to a human subject.
- the nutritional supplement may be administered from one to three times daily or. alternatively, may be administered every other day, or may be administered once a week.
- the nutritional supplement may be administered on an empty stomach.
- the composition may be administered topically on the skin.
- the nutritional supplement of the third embodiments is essentially limited to the aforementioned ingredients and does not include any additional active ingredients intended to add nutritional content (e.g., vitamins, minerals, etc.), but may include additional ingredients not intended to add nutritional content such as ingredients intended to fulfill a non-nutritional purpose (e.g., coloring, fillers, flavoring, an ingredient for maintaining the structural form, etc.).
- additional active ingredients intended to add nutritional content
- additional ingredients not intended to add nutritional content such as ingredients intended to fulfill a non-nutritional purpose (e.g., coloring, fillers, flavoring, an ingredient for maintaining the structural form, etc.).
- Each ingredient of the nutritional supplement of the present invention may be prepared in accordance with any method known to one of ordinary skill in the art. Alternatively, each ingredient may be obtained in a fully prepared from a commercially available source.
- the nutritional supplement of the present invention may be in any suitable oral administration form, including but not limited to: a chewable form, a liquid form, a spray form, a capsule form, a suppository form, dissolvable wafer, and a powder form.
- the ingredients of the nutritional supplement may be distributed homogeneously or non-homogeneously within the nutritional supplement.
- the nutritional supplement of the present invention may be ingested on a regular basis, such as a daily or weekly intake at a dosage tailored to an individual's needs; i.e., the nutritional supplement is to be taken regularly as multiples (l x, 2x, etc.) of the structural units (pills, tablets, capsules, liquid dose, etc.) in accordance with the needs of the individual.
- the nutritional supplement of the present invention may be ingested on an as-needed basis at a dosage tailored to the individual's needs. Medical or nutritional counseling may be beneficial for arriving at a desirable or optimal dosage tailored to the individual's needs. Topical delivery systems such as lotions and creams may apply.
- test products were tested on their solubility in cell culture media or DMSO (in that order). Starting from doses of 200 mg/mL the test products were diluted stepwise until totally solved. Since no effect of the test product at concentrations w ere expected below 2 mg/mL we did not dilute further than that regardless if fully dissolved or not. Test products that did not dissolve in DMSO at a concentration of 2 mg/mL were tested in cell culture media in a suspension of 2 mg/mL. Marine proteoglycans samples demonstrated a maximum solubility concentration of 100 mg/ml. Type I (bovine) collagen samples demonstrated a maximum solubility concentration of 20 mg/ml.
- Marine proteoglycans samples were tested at concentrations ranging from 0.01 to 100 mg/ml. The highest concentration with more than 70% viability was 0.01 mg/ml.
- Type I collagen samples were tested at concentrations ranging from 0.2 to 20 mg/ml. The highest concentrarion w ith more than 70% viability 7 was 20 mg/ml and was nontoxic at all tested concentrations.
- Keratinocytes were seeded in 3000 cells/well onto 96-well plates and were treated with a dose of the test product causing no loss of viability 7 greater than 90% as evalutated in 2.2. 24h after seeding.
- the cells were cultured for a maximum of 72 hours to cover more than 70% (up to 90%) of the total growth area. This was done to prevent slowing down of proliferation due to contact inhibition effects.
- a second run was conducted (if necessary) due to toxic effects of combinations or other unexpected events.
- Relative cell numbers at the end of the treatment again were determined by the addition of MTT. Results were generated by absorbance measurement of the blue metabolite formed. The results were presented in tabular form including mean, standard deviation and significance of differences (if applicable).
- Marine proteoglycans applied at a concentration of 0.01 mg/ml resulted in a mean value of 99.5% proliferation of skin cells relative to the control when measured at 72 hours.
- Type I collagen applied at a concentration of 6 mg/ml resulted in a mean value of 102.7% proliferation of skin cells relative to the control with a mean P value of 0.05 when measured at 72 hours.
- the application of the combined type I collagen/marine proteoglycans applied at a respective concentration of 6mg/0.01mg resulted in a mean value of 134.3% proliferation of skin cells with a P value of 0.001 relative to the control when measured at 72 hours.
- the latter represents a P value that is 50 times more significant.
- the application of the combined type I collagen/marine proteoglycans applied at a respective concentration of 0.3mg/0.01mg resulted in a mean value of 132% proliferation of skin cells with a P value of 0.001 relative to the control when measured at 72 hours, with the same significant P value.
- the application of the combined type I collagen/marine proteoglycans applied at a respective concentration of O.lmg/O.Olmg resulted in a mean value of 128% proliferation of skin cells with a P value of 0.01 relative to the control when measured at 72 hours, representing a P value that is 10 times more significant.
- the immortal cell line HaCat which is a keratinocyte derived cell line.
- the cell line is stable, not of carcinogenic origin and retains many properties of normal keratinocytes.
- Tissue Model The testing determines how exposure to the test materials ⁇ TMs) will influence mRNA expression in in vitro cell tissue samples. Changes in genes will be expressed relative to a suitable Vehicle Controls alone and in mixtures.
- the study is performed using full -thickness EFT-400 in vitro skin tissues comprised of normal human keratinocytes in a stratified comeal layer, and a dermal component containing an intact dermal-epidermal junction (DEJ) and viable fibroblasts.
- EFT-400 in vitro skin tissues comprised of normal human keratinocytes in a stratified comeal layer, and a dermal component containing an intact dermal-epidermal junction (DEJ) and viable fibroblasts.
- DEJ dermal-epidermal junction
- RNASeq Differential Gene Expression ⁇ RNASeq
- the analysis is performed using an Illumina NextSeq 550 Dx instrument. A read depth of 25M reads per sample. Data analysis is performed to identify statistically significant changes in gene expression.
- the results will show thousands of skin gene marker expressions at ranges from 1% to 10% marine proteoglycans to 90 % to 99% collagen, several of which are significant to skin growth.
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- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
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Abstract
A composition comprising marine proteoglycans and collagen, which stimulates the growth of skin cells. Methods of stimulating skin cell growth comprise administering the novel composition to a human subject.
Description
HERBAL FORMULATION FOR IMPROVEMENT OF SKIN GROWTH
PRIORITY CLAIM
This application claims the benefit of the filing date of United States Provisional Patent Application Serial Number 63/421 ,910, filed November 2, 2022 for HERBAL FORMULATION FOR IMPROVEMENT OF SKIN GROWTH which are incorporated herein in its entirety.
TECHNICAL FIELD
The present invention relates to a nutritional supplement composition comprising marine proteoglycans and collagen that can be administered to a human subject to stimulate skin cell growth. The nutritional supplement can be administered in an oral form or as a topical agent.
The present invention relates to methods of stimulating or promoting skin cell growth in the face or any selected areas of the body. More specifically, the method comprises administering the nutritional supplement composition to a human subject in order to stimulate or promote skin cell growth.
DESCRIPTION OF THE ART
Skin is composed of the epidermis and the dermis. Below these layers lies the hypodermis, which is not usually classified as a layer of skin. The hypodermis is also commonly referred to as subcutaneous fat layer, or subcutaneous tissue. The outermost epidermis is made up of stratified squamous epithelium with an underlying basement membrane. It contains no blood vessels and is nourished by diffusion from the dermis. The main type of cells which make up the epidermis are keratinocytes, with melanocytes and langerhans cells also present. This layer of skin is responsible for keeping w ater in the body and keeping other harmful chemicals and pathogens out.
The dermis lies below the epidermis and contains a number of structures including blood vessels, nerves, hair follicles, smooth muscle, glands and lymphatic tissue. The dermis (or corium) is typically 3-5 mm thick and is the major component of human skin. It is composed of a network of connective tissue, predominantly collagen fibrils providing support and elastic tissue providing flexibility. The main cell types are
fibroblasts, adipocytes (fat storage) and macrophages. The hypodermis lies below the dermis. Its purpose is to attach the skin to underlying bone and muscle as well as supplying it with blood vessels and nerves. It is made up of loose connective tissue and elastin. The main cell types are fibroblasts, macrophages and adipocytes. The hypodermis contains 50% body fat. Fat serves as padding and insulation for the body.
Skin aging (e.g., facial aging) occurs as the result of several factors: inherent changes within the skin, effects of gravity, facial muscles acting on the skin (dynamic lines), soft tissue loss or shift and bone loss and loss of tissue elasticity’. The skin ages when the epidermis begins to thin, causing the junction with the dermis to flatten. Collagen decreases as a person ages and the bundles of collagen, which gives the skin turgor, become looser and lose strength. When the skin loses elasticity, it is less able to resist stretching. Coupled with gravity, muscle pull and tissue changes, the skin begin to wrinkle. Loss of skin cells and loss of bonds between cells also reduces the barrier function of the skin, w hich can cause the skin's pore size to increase.
Although various injectables have been developed and used clinically for restoration of age-related tissue loss in the face, due to various limitations in the materials or compatibility with the tissues, the long term effect in restoring the tissue loss is limited. It is desirable to develop improved compositions and treatment methods to enhance the overall effects in restoration of age-related tissue loss in the face or selected areas of the body, such as neck and hands, by stimulating or promoting skin cell growth.
DETAILED DESCRIPTION AND EXAMPLES
The present invention is a nutritional supplement. It is a novel composition comprising marine proteoglycans and collagen, which stimulates the growth of skin cells.
A particular embodiment of the present disclosure relates to an oral nutritional supplement that includes the novel composition. The composition may be delivered as non-toxic salts thereof, effective complexes thereof, stable chelates thereof, active esters thereof, functional derivatives thereof, and mixtures thereof which are effective to stimulate skin cell growth in the general population.
Another particular embodiment relates to a topical nutritional supplement that comprises a mixture of marine proteoglycans and type I collagen. In further embodiments, the type I collagen is bovine, porcine, or marine collagen.
Methods of stimulating skin cell growth comprise administering the novel composition to a human subject.
The composition will find applications to stimulate skin cell growth and to promote skin tissue growth, repair the skin, or to rebalance skin proliferation.
In embodiments of the invention, the nutritional supplement includes a composition for promoting skin cell growth comprising marine proteoglycans (obtained from fish cartilage) and collagen in a ratio of 0.1% to 10% marine proteoglycans to 90% to 99.9% collagen. In a particular embodiment, the composition comprises marine proteoglycans and collagen in a ration of 0.1% to 99.9%. In another embodiment, the composition comprises marine proteoglycans and collagen in a ration of 10% to 90%. In particular embodiments of the invention, the collagen may be type I collagen and, more specifically, can be bovine collagen.
In another embodiment, a method of promoting skin cell grow th comprises administering the nutritional supplement to a human subject.
Particular embodiments of the invention relate to oral administration of the disclosed nutritional supplement to a human. The nutritional supplement may be administered from one to three times daily or. alternatively, may be administered every other day, or may be administered once a week. In particular embodiments, the nutritional supplement may be administered on an empty stomach. In another embodiment of the invention, the composition may be administered topically on the skin.
In accordance with the “consist essentially of' and “consisting essentially of' language, the nutritional supplement of the third embodiments is essentially limited to the aforementioned ingredients and does not include any additional active ingredients intended to add nutritional content (e.g., vitamins, minerals, etc.), but may include additional ingredients not intended to add nutritional content such as ingredients intended to fulfill a non-nutritional purpose (e.g., coloring, fillers, flavoring, an ingredient for maintaining the structural form, etc.).
Each ingredient of the nutritional supplement of the present invention may be prepared in accordance with any method known to one of ordinary skill in the art. Alternatively, each ingredient may be obtained in a fully prepared from a commercially available source.
The nutritional supplement of the present invention may be in any suitable oral administration form, including but not limited to: a chewable form, a liquid form, a spray form, a capsule form, a suppository form, dissolvable wafer, and a powder form.
Irrespective of the structural form of the nutritional supplement, the ingredients of the nutritional supplement may be distributed homogeneously or non-homogeneously within the nutritional supplement.
The nutritional supplement of the present invention may be ingested on a regular basis, such as a daily or weekly intake at a dosage tailored to an individual's needs; i.e., the nutritional supplement is to be taken regularly as multiples (l x, 2x, etc.) of the structural units (pills, tablets, capsules, liquid dose, etc.) in accordance with the needs of the individual. Alternatively, the nutritional supplement of the present invention may be ingested on an as-needed basis at a dosage tailored to the individual's needs. Medical or nutritional counseling may be beneficial for arriving at a desirable or optimal dosage tailored to the individual's needs. Topical delivery systems such as lotions and creams may apply.
EXAMPLES
Example 1 - Solubility
The solubility of the test products in cell culture media were assessed in accordance with ICCVAM Test Method Evaluation Report Appendix C (November 2006). Briefly, test products were tested on their solubility in cell culture media or DMSO (in that order). Starting from doses of 200 mg/mL the test products were diluted stepwise until totally solved. Since no effect of the test product at concentrations w ere expected below 2 mg/mL we did not dilute further than that regardless if fully dissolved or not. Test products that did not dissolve in DMSO at a concentration of 2 mg/mL were tested in cell culture media in a suspension of 2 mg/mL.
Marine proteoglycans samples demonstrated a maximum solubility concentration of 100 mg/ml. Type I (bovine) collagen samples demonstrated a maximum solubility concentration of 20 mg/ml.
Five concentrations of each test product in solution were tested with keratinocytes for 72 hours on 96-well plates. The relative number of viable cells after the treatment were evaluated by addition of a vital dye (MTT). The dye was transformed to a blue metabolite by living cells only. The absorbance measurement of the blue dye generated numbers representative to the amount of living cells in each single culture. Doses that exhibited no loss of viability greater than 70% (compared to the untreated control) were classified as nontoxic and thus applicable in the proliferation assay. However, in the current approach, concentrations were chosen that only resulted in more than 80% viability7.
Marine proteoglycans samples were tested at concentrations ranging from 0.01 to 100 mg/ml. The highest concentration with more than 70% viability was 0.01 mg/ml.
Type I collagen samples were tested at concentrations ranging from 0.2 to 20 mg/ml. The highest concentrarion w ith more than 70% viability7 was 20 mg/ml and was nontoxic at all tested concentrations.
Example 3 - Proliferation assay
Keratinocytes were seeded in 3000 cells/well onto 96-well plates and were treated with a dose of the test product causing no loss of viability7 greater than 90% as evalutated in 2.2. 24h after seeding. The cells were cultured for a maximum of 72 hours to cover more than 70% (up to 90%) of the total growth area. This was done to prevent slowing down of proliferation due to contact inhibition effects. A second run was conducted (if necessary) due to toxic effects of combinations or other unexpected events. Relative cell numbers at the end of the treatment again were determined by the addition of MTT. Results were generated by absorbance measurement of the blue metabolite
formed. The results were presented in tabular form including mean, standard deviation and significance of differences (if applicable).
Marine proteoglycans applied at a concentration of 0.01 mg/ml resulted in a mean value of 99.5% proliferation of skin cells relative to the control when measured at 72 hours. Type I collagen applied at a concentration of 6 mg/ml resulted in a mean value of 102.7% proliferation of skin cells relative to the control with a mean P value of 0.05 when measured at 72 hours.
Surprisingly, the application of the combined type I collagen/marine proteoglycans applied at a respective concentration of 6mg/0.01mg resulted in a mean value of 134.3% proliferation of skin cells with a P value of 0.001 relative to the control when measured at 72 hours. The latter represents a P value that is 50 times more significant. Likewise, the application of the combined type I collagen/marine proteoglycans applied at a respective concentration of 0.3mg/0.01mg resulted in a mean value of 132% proliferation of skin cells with a P value of 0.001 relative to the control when measured at 72 hours, with the same significant P value. Additionally, the application of the combined type I collagen/marine proteoglycans applied at a respective concentration of O.lmg/O.Olmg resulted in a mean value of 128% proliferation of skin cells with a P value of 0.01 relative to the control when measured at 72 hours, representing a P value that is 10 times more significant.
Example 4 - Cell model
We applied the immortal cell line HaCat which is a keratinocyte derived cell line. The cell line is stable, not of carcinogenic origin and retains many properties of normal keratinocytes.
Example 5- Gene Expression Testing
The testing determines how exposure to the test materials {TMs) will influence mRNA expression in in vitro cell tissue samples. Changes in genes will be expressed relative to a suitable Vehicle Controls alone and in mixtures.
Tissue Model
The study is performed using full -thickness EFT-400 in vitro skin tissues comprised of normal human keratinocytes in a stratified comeal layer, and a dermal component containing an intact dermal-epidermal junction (DEJ) and viable fibroblasts.
Exposure Method
A final volume of 15 pL of the test material is applied to the surface of the cell tissue following equilibration and again 24 hrs. following the first application. Cell Tissues are collected 24 hrs. after the second application (total exposure time= 48 hrs.).
Differential Gene Expression Analysis
High quality RNA is utilized to test for the RNASeq analysis. Samples that meet the criteria are processed for Differential Gene Expression {RNASeq) analysis.
Differential Gene Expression (DE) is performed using a stranded mRNA-based sequencing approach using Nextgen Sequencing {NGS) (Illumina, cat#:20040532) . This approach enables a highly sensitive and accurate method for quantifying gene expression and is ideal for identifying both known and novel gene transcripts.
The analysis is performed using an Illumina NextSeq 550 Dx instrument. A read depth of 25M reads per sample. Data analysis is performed to identify statistically significant changes in gene expression.
The results will show thousands of skin gene marker expressions at ranges from 1% to 10% marine proteoglycans to 90 % to 99% collagen, several of which are significant to skin growth.
Claims
1. A composition for promoting skin cell growth, comprising: marine proteoglycans and collagen in a ratio of 0.1% to 3% marine proteoglycans to 99.9% to 97% collagen given to a mammal or human.
2. A composition for promoting skin cell growth, comprising: marine proteoglycans and collagen in a ratio of 5% marine proteoglycans to 95% collagen given to a mammal or human.
3. A composition for promoting skin cell growth, comprising: marine proteoglycans and collagen in a ratio of 10% marine proteoglycans to 90% collagen given to a mammal or human.
4. A composition for promoting skin cell growth, comprising: marine proteoglycans and collagen in a ratio of .01 to 10% marine proteoglycans to 90% to 99.99 collagen given to a mammal or human.
5. The composition of claim 1, wherein the marine proteoglycans and collagen are in a ration of 0.1% to 99.9% given to a mammal or human.
6. The composition of claims 1-5, wheiren the collagen is a type I collagen.
7. The composition of claim 6, wheiren the t pe I collagen is bovine , porcine, or marine collagen.
8. The composition of claim 1, wherein the composition is formulated as an oral agent.
9. The composition of claim 1, wherein the composition is formulated as a chewable form, a liquid form, a spray form, lotion form, cream form, a capsule form, dissolvable wafer, or a powder form.
10. The composition of claim 1, wherein the composition may be delivered as complexes thereof, stable chelates thereof, active esters thereof, functional derivatives thereof, and mixtures thereof.
11. The composition of claim 1, wherein the composition is formulated as a topical agent.
12. A method of promoting skin cell growth, comprising administering the composition of claim 1 to a mammal or human subject.
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US202263421910P | 2022-11-02 | 2022-11-02 | |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06179612A (en) * | 1992-07-27 | 1994-06-28 | Nonogawa Shoji Kk | Cosmetic |
US20130310540A1 (en) * | 2011-01-19 | 2013-11-21 | Sunstar Inc. | Extract of aquatic animal cartilage |
US20140080761A1 (en) * | 2009-07-16 | 2014-03-20 | Hirosaki University | Proteoglycan-containing material |
WO2015083630A1 (en) * | 2013-12-04 | 2015-06-11 | サントリーホールディングス株式会社 | Composition comprising collagen peptide, elastin peptide and proteoglycan |
KR20210039636A (en) * | 2019-10-02 | 2021-04-12 | 휴젤(주) | Cosmetic composition for skin moisture and manufacturing method thereof |
-
2023
- 2023-10-31 WO PCT/US2023/078280 patent/WO2024097704A1/en unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06179612A (en) * | 1992-07-27 | 1994-06-28 | Nonogawa Shoji Kk | Cosmetic |
US20140080761A1 (en) * | 2009-07-16 | 2014-03-20 | Hirosaki University | Proteoglycan-containing material |
US20130310540A1 (en) * | 2011-01-19 | 2013-11-21 | Sunstar Inc. | Extract of aquatic animal cartilage |
WO2015083630A1 (en) * | 2013-12-04 | 2015-06-11 | サントリーホールディングス株式会社 | Composition comprising collagen peptide, elastin peptide and proteoglycan |
KR20210039636A (en) * | 2019-10-02 | 2021-04-12 | 휴젤(주) | Cosmetic composition for skin moisture and manufacturing method thereof |
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