CN110604701A - Composition for promoting collagen proliferation - Google Patents
Composition for promoting collagen proliferation Download PDFInfo
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- CN110604701A CN110604701A CN201810621676.0A CN201810621676A CN110604701A CN 110604701 A CN110604701 A CN 110604701A CN 201810621676 A CN201810621676 A CN 201810621676A CN 110604701 A CN110604701 A CN 110604701A
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- composition
- hyaluronic acid
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- gold
- collagen proliferation
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- 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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- 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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/413—Nanosized, i.e. having sizes below 100 nm
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/91—Injection
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Medicinal Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Birds (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The commercially available hyaluronic acid injection (gel) has safety concern due to the cross-linking agent, but the hyaluronic acid injection without the cross-linking agent can only be maintained in the human body for 1-2 days. In order to obtain hyaluronic acid injection which does not contain a cross-linking agent and can be maintained in a human body for more than 7 days, the inventor mixes a plurality of gold foils and non-cross-linked hyaluronic acid into a composition for promoting collagen proliferation, particularly according to a weight ratio. Also, animal experiments confirmed that, when an adult dose of 6.66mL of the collagen proliferation promoting composition solution was administered to a skin site of a mouse by subcutaneous injection, collagen proliferation efficacy was exhibited in connective tissues of the skin site. Obviously, the composition for promoting collagen proliferation has the potential of simultaneously replacing the existing hyaluronic acid injection and/or collagen filling injection.
Description
Technical Field
The invention relates to the biotechnological field, in particular, a composition promoting protoprotein proliferation.
Background
Injection cosmetology (Injection cosmetology) utilizes a syringe to inject a biocompatible material into the dermis or subcutaneous tissue to achieve the desired sculpting of a specific area of the human body or to reduce wrinkles in the specific area. Commonly used biocompatible materials include: autologous fat, hyaluronic acid, collagen, hydroxyl apatite, megalactic acid, polymethyl methacrylate and polyacrylamide. Wherein, the hyaluronic acid molecules are connective tissue components in the dermis layer, and viscoelastic fluid is formed at the chimeric part of the collagen and the elastin fiber.
As the skin ages, the amount of hyaluronic acid in the dermis is reduced. Thus, injection of hyaluronic acid is now one of the most commonly used micro-plastic surgeries, often used to improve facial wrinkles and lip sculpting. Unfortunately, hyaluronic acid is maintained in a natural state for only 1 to 2 days, and then gradually degraded and then metabolized by the human body. Therefore, the hyaluronic acid injection currently available in the market is usually in the form of gel, which is composed of hyaluronic acid, a cross-linking agent and a buffer solution. Common crosslinkers are, for example, 1,4-butanediol glycidyl ether (1,4-butanediol diglycidyl ether, BDDE). The following description will more clearly explain the process of commercially available hyaluronic acid injection. Firstly, saccharides are added into a bacterial liquid of streptococcus equi, and the bacterial liquid can generate hyaluronic acid after fermentation. After hyaluronic acid is extracted from the bacterial liquid by using an organic solvent, BDDE and hyaluronic acid are subjected to a crosslinking reaction, and then high-concentration crosslinked hyaluronic acid can be obtained; finally, the concentration of the cross-linked hyaluronic acid is adjusted by using a buffer solution, and then the hyaluronic acid injection is obtained.
During the crosslinking reaction, the BDDE content can directly influence the crosslinking degree of the hyaluronic acid. It is worth noting that BDDE is not a safe product by itself, but after the crosslinking reaction with hyaluronic acid is completed, BDDE can be metabolized by the body along with hyaluronic acid. However, commercially available hyaluronic acid injection does not only contain fully crosslinked BDDE, but also contains not fully crosslinked BDDE and not crosslinked BDDE. It is thought that these incompletely crosslinked BDDE and uncrosslinked BDDE become unsafe factors in hyaluronic acid injection. Therefore, the government has regulated that commercially available hyaluronic acid injection (gel) must clearly indicate the proportion of BDDE contained. Even so, for doctors in the medical and aesthetic clinics or patients receiving injection cosmetics, there is still no sufficient understanding of how much incompletely crosslinked BDDE and/or uncrosslinked BDDE is contained in the hyaluronic acid injection (gel) used.
In another aspect, the use of injected collagen comprises: reducing wrinkle depth, repairing scar, filling concave hole, improving nose shape, reconstructing chin, beautifying lip, increasing earlobe, and moistening cheek. However, when the physician evaluates the efficacy of the injection, the physician needs to consider whether the consumer is allergic to collagen, so as to avoid the discomfort caused by the injection of collagen.
From this, it is known how to effectively delay the degradation of hyaluronic acid in the human body with or without using a crosslinking agent, and the most important issue is currently being addressed. Meanwhile, it is also a remarkable research direction to develop a subcutaneous filling material with collagen production promoting effect by using hyaluronic acid as a base material. In view of the above, the present inventors have made intensive studies and, as a result, have completed development of the composition for promoting collagen proliferation of the present invention.
Disclosure of Invention
The commercially available hyaluronic acid injection (gel) has safety concern due to the cross-linking agent, but the hyaluronic acid injection without the cross-linking agent can only be maintained in the human body for 1-2 days. Therefore, the main objective of the present invention is to provide a composition for promoting collagen proliferation, which is prepared by mixing a plurality of gold foils and an uncrosslinked hyaluronic acid according to a weight ratio. Also, animal experiments confirmed that the collagen proliferation efficacy can be exhibited in the connective tissue of a skin site of a warm-blooded animal having hair follicles by administering 6.66mL of the collagen proliferation promoting composition solution to the skin site by subcutaneous injection at an adult dose. Obviously, the composition for promoting collagen proliferation has the potential of simultaneously replacing the existing hyaluronic acid injection and/or collagen filling injection.
To achieve the above-mentioned objectives, the present inventors provide an embodiment of the composition for promoting collagen proliferation, which comprises:
an uncrosslinked hyaluronic acid; and
gold foils (gold flakes) stacked by physical vapor deposition of gold nanoparticles having a particle size of 2nm to 30nm and having a gold foil thickness ranging from 40nm to 200 nm;
wherein, the hyaluronic acid and the gold foils have a weight ratio between 1:1 and 10: 1.
In order to achieve the above-mentioned objectives of the present invention, the present inventors also provide another embodiment of the composition for promoting collagen proliferation, which comprises:
an uncrosslinked hyaluronic acid; and
gold foils (gold flakes) stacked by physical vapor deposition of gold nanoparticles having a particle size of 2nm to 30nm and having a gold foil thickness ranging from 40nm to 200 nm;
wherein, the hyaluronic acid and the gold foils have a weight ratio between 1:1 and 1: 7.
Drawings
FIG. 1 is a schematic view showing a process of preparing a composition for promoting collagen proliferation according to the present invention;
FIG. 2 is a photograph showing H & E staining of tissue sections of various groups of mice;
FIG. 3 is an image showing MT staining of tissue sections of various groups of mice; and
FIG. 4 is a photograph showing the MT staining after enlargement.
Wherein the reference numerals are:
composition for promoting collagen proliferation
11 hyaluronic acid
12 gold foil
Detailed Description
In order to more clearly describe the composition for promoting collagen proliferation of the present invention, the following description will be made in detail with reference to the accompanying drawings.
First embodiment
Referring to fig. 1, a schematic process diagram of a composition for promoting collagen proliferation according to the present invention is shown. As shown in fig. 1, a first embodiment of the collagen proliferation promoting composition 1 of the present invention comprises: an uncrosslinked hyaluronic acid 11 and a plurality of gold foils 12(gold flakes). Specifically, each gold foil 12 is formed by stacking a plurality of nano-gold particles with a particle size between 2nm and 30nm through a physical vapor deposition process, and has a gold foil thickness ranging between 40nm and 200nm and a gold foil width greater than 0.01 mm. Also, in the first embodiment, the hyaluronic acid 11 and the gold foils 12 have a weight ratio ranging from 1:1 to 10: 1. As shown in FIG. 1, in the preparation of the composition 1 for promoting collagen proliferation, the hyaluronic acid 11 powder can be dissolved in a liquid to obtain a hyaluronic acid solution, and the concentration of the hyaluronic acid solution can be adjusted at the same time. For example, 100mg of hyaluronic acid powder can be dissolved in 10mL of pure water to obtain 1% hyaluronic acid solution. Then, a plurality of gold foils 12 were mixed into the hyaluronic acid solution, thereby obtaining the composition 1 for promoting collagen proliferation of the present invention.
Of course, it is also possible to mix a plurality of gold foils 12 into 10mL of pure water (i.e., solution), and then add 100mg of hyaluronic acid powder into 10mL of pure water mixed with a plurality of gold foils 12, so that the collagen proliferation promoting composition 1 of the present invention can be obtained as well. On the other hand, commercially available hyaluronic acid solution can be purchased as it is. It must be noted that some hyaluronic acid solutions consist of make-up water and hyaluronic acid powder. However, the collagen proliferation promoting composition 1 of the present invention is administered (applied) by subcutaneous injection, and therefore, it is preferable to purchase a hyaluronic acid solution consisting of pure water and hyaluronic acid powder.
Second embodiment
Referring to fig. 1 repeatedly, the second embodiment of the collagen proliferation promoting composition 1 of the present invention also comprises: an uncrosslinked hyaluronic acid 11 and a plurality of gold foils 12(gold flakes). In contrast, in the second embodiment, the weight ratio between the hyaluronic acid 11 and the gold foils 12 is between 1:1 and 1: 7.
Animal experiments
To verify that the composition 1 for promoting collagen proliferation does have the effect of promoting collagen proliferation, the inventors specifically designed and completed an animal experiment. Referring to Table (1) below, the test animals selected for the animal experiments were mice, and the mice were divided into Blank group (Blank), 1:1 group, 1:6.88 group, 10:1 group, and HA group. Also, the skilled engineer familiar with animal experimental design can confirm from table (1) that the groups 1:1 and 10:1 were used to verify whether the first embodiment of the collagen proliferation promoting composition 1 had indeed the effect of promoting collagen proliferation. On the other hand, the 1:1 and 1:6.88 groups were used to verify whether the second embodiment of the collagen proliferation promoting composition 1 had indeed the effect of promoting collagen proliferation.
Watch (1)
In animal experiments, the corresponding test sample was administered to a skin site of a mouse by subcutaneous injection. After the tissue sections of the skin part were taken on days 7 and 27, the tissue sections were subjected to hematoxylin-eosin staining (H & E stain) and Masson trichrome staining (MT stain), respectively. Fig. 2 is an image showing H & E staining of tissue sections of the respective groups of mice, and fig. 3 is an image showing MT staining of tissue sections of the respective groups of mice. In the image of FIG. 2, the epidermis, hair follicle and sebaceous gland (or fat), less mature connective tissue, more mature coated connective tissue, implant (i.e., gold foil), and subcutaneous muscle (bundle) of the skin region of the mouse are shown from top to bottom, respectively.
Continuing to refer to FIG. 3, and referring to FIG. 4, an enlarged MT stained image is shown. In fig. 4, the solid arrows indicate the implant (i.e., gold foil) and the dashed arrows indicate collagen. Obviously, the experimental data confirmed that collagen was significantly proliferated around the gold foil 12 after 7 days from the injection of the solution of the collagen proliferation promoting composition 1 consisting of the uncrosslinked hyaluronic acid 11 and the gold foil 12 in a specific ratio into the skin of the mouse. Further, after 27 days of completing the subcutaneous injection, the continuously proliferated collagen would fill the gap between the gold foil 12 and the gold foil 12.
Therefore, animal experiments confirmed that, after an adult dose of 6.66mL of the collagen proliferation promoting composition 1 solution was administered to a skin site of a subject by subcutaneous injection, collagen proliferation efficacy was exhibited in the connective tissue of the skin site after 7 days. Wherein the individual is a warm-blooded animal having hair follicles.
Thus, the composition 1 for promoting collagen proliferation according to the present invention is fully and clearly illustrated above, and thus, the following advantages can be obtained:
(1) the commercially available hyaluronic acid injection (gel) has safety concern due to the cross-linking agent, but the hyaluronic acid injection without the cross-linking agent can only be maintained in the human body for 1-2 days. In order to derive a hyaluronic acid injection which does not contain a cross-linking agent and can be maintained in a human body for more than 7 days, the inventors of the present invention particularly mix a plurality of gold foils 12 and an uncrosslinked hyaluronic acid 11 according to a weight ratio to form a composition for promoting collagen proliferation. Also, animal experiments confirmed that, after an adult dose of 6.66mL of the solution of the collagen proliferation promoting composition 1 was administered to a skin site of a warm-blooded animal having hair follicles by subcutaneous injection, collagen proliferation efficacy was exhibited in connective tissues of the skin site. It is worth emphasizing that the shown efficacy of collagen proliferation can be maintained for at least 27 days.
(2) Based on the above, it is obvious that the composition 1 for promoting collagen proliferation of the present invention has the potential of simultaneously replacing the existing hyaluronic acid injection and/or collagen filling injection.
It should be emphasized that the above detailed description is specific to possible embodiments of the invention, but this is not to be taken as limiting the scope of the invention, and all equivalent implementations or modifications that do not depart from the technical spirit of the invention are intended to be included within the scope of the present invention.
Claims (12)
1. A composition for promoting collagen proliferation, comprising:
an uncrosslinked hyaluronic acid; and
gold foils (gold flakes) stacked by physical vapor deposition of gold nanoparticles having a particle size of 2nm to 30nm and having a gold foil thickness ranging from 40nm to 200 nm;
wherein, the hyaluronic acid and the gold foils have a weight ratio between 1:1 and 10: 1.
2. The composition for promoting collagen proliferation as claimed in claim 1, further comprising a liquid for mixing with the gold foils to form a liquid gold foil (collagen gold flakes); and the liquid is simultaneously used for adjusting the concentration of the hyaluronic acid.
3. The composition for promoting collagen proliferation as claimed in claim 1, further comprising a liquid for adjusting the concentration of hyaluronic acid.
4. The composition for promoting collagen proliferation according to claim 1, wherein the width of the plurality of gold foils is greater than 0.01 mm.
5. The collagen proliferation promoting composition according to claim 2, wherein the collagen proliferation promoting composition is administered to a skin site of a subject by subcutaneous injection in an amount of 6.66mL of the solution, and the collagen proliferation promoting composition exhibits collagen proliferation effect in connective tissue of the skin site.
6. A composition for promoting collagen proliferation as claimed in claim 5, wherein the individual is a warm-blooded animal having hair follicles.
7. A composition for promoting collagen proliferation, comprising:
an uncrosslinked hyaluronic acid; and
gold foils (gold flakes) stacked by physical vapor deposition of gold nanoparticles having a particle size of 2nm to 30nm and having a gold foil thickness ranging from 40nm to 200 nm;
wherein, the hyaluronic acid and the gold foils have a weight ratio between 1:1 and 1: 7.
8. The composition for promoting collagen proliferation as claimed in claim 7, further comprising a liquid for mixing with the gold foils to form a liquid gold foil (collagen gold flakes); and the liquid is simultaneously used for adjusting the concentration of the hyaluronic acid.
9. The composition for promoting collagen proliferation as claimed in claim 7, further comprising a liquid for adjusting the concentration of hyaluronic acid.
10. The composition for promoting collagen proliferation according to claim 7, wherein the width of the gold foils is greater than 0.01 mm.
11. The collagen proliferation promoting composition according to claim 8, wherein the collagen proliferation promoting composition is administered to a skin site of a subject by subcutaneous injection in an amount of 6.66mL of the solution, and the collagen proliferation promoting composition exhibits collagen proliferation effect in connective tissue of the skin site.
12. A composition for promoting collagen proliferation as claimed in claim 11, wherein the individual is a warm-blooded animal having hair follicles.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810621676.0A CN110604701A (en) | 2018-06-15 | 2018-06-15 | Composition for promoting collagen proliferation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810621676.0A CN110604701A (en) | 2018-06-15 | 2018-06-15 | Composition for promoting collagen proliferation |
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| CN110604701A true CN110604701A (en) | 2019-12-24 |
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| CN201810621676.0A Pending CN110604701A (en) | 2018-06-15 | 2018-06-15 | Composition for promoting collagen proliferation |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1381608A (en) * | 2001-04-20 | 2002-11-27 | 京华堂实业股份有限公司 | Process for preparing high-purity gold foil |
| CN101502675A (en) * | 2008-02-04 | 2009-08-12 | 山东省药学科学院 | Suspension of hyaluronic acid or salt thereof containing macromolecule hydrogel for injection and preparation method thereof |
| TW201124178A (en) * | 2010-01-13 | 2011-07-16 | jun-rong Huang | Fillings for injection. |
| TW201139691A (en) * | 2010-05-11 | 2011-11-16 | Univ China Medical | Nanometal dispersion and method for preparing the same |
| CN105853250A (en) * | 2016-05-13 | 2016-08-17 | 诺斯贝尔化妆品股份有限公司 | Cosmetic composition containing gold collagen |
| KR101682933B1 (en) * | 2016-07-14 | 2016-12-06 | 이정현 | Skin filling composition containing gold |
-
2018
- 2018-06-15 CN CN201810621676.0A patent/CN110604701A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1381608A (en) * | 2001-04-20 | 2002-11-27 | 京华堂实业股份有限公司 | Process for preparing high-purity gold foil |
| CN101502675A (en) * | 2008-02-04 | 2009-08-12 | 山东省药学科学院 | Suspension of hyaluronic acid or salt thereof containing macromolecule hydrogel for injection and preparation method thereof |
| TW201124178A (en) * | 2010-01-13 | 2011-07-16 | jun-rong Huang | Fillings for injection. |
| TW201139691A (en) * | 2010-05-11 | 2011-11-16 | Univ China Medical | Nanometal dispersion and method for preparing the same |
| CN105853250A (en) * | 2016-05-13 | 2016-08-17 | 诺斯贝尔化妆品股份有限公司 | Cosmetic composition containing gold collagen |
| KR101682933B1 (en) * | 2016-07-14 | 2016-12-06 | 이정현 | Skin filling composition containing gold |
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Application publication date: 20191224 |