WO2022100519A1 - 具有促渗透作用的透明质酸组合物、制备方法及其应用 - Google Patents
具有促渗透作用的透明质酸组合物、制备方法及其应用 Download PDFInfo
- Publication number
- WO2022100519A1 WO2022100519A1 PCT/CN2021/128882 CN2021128882W WO2022100519A1 WO 2022100519 A1 WO2022100519 A1 WO 2022100519A1 CN 2021128882 W CN2021128882 W CN 2021128882W WO 2022100519 A1 WO2022100519 A1 WO 2022100519A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hyaluronic acid
- salt
- composition
- acid composition
- acetylated
- Prior art date
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- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical group NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 claims description 24
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- 235000013793 astaxanthin Nutrition 0.000 claims description 19
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 claims description 19
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- YUZJJFWCXJDFOQ-UHFFFAOYSA-K manganese(3+);2-methoxy-6-[2-[(3-methoxy-2-oxidophenyl)methylideneamino]ethyliminomethyl]phenolate;chloride Chemical compound [Cl-].[Mn+3].COC1=CC=CC(C=NCCN=CC=2C(=C(OC)C=CC=2)[O-])=C1[O-] YUZJJFWCXJDFOQ-UHFFFAOYSA-K 0.000 claims description 5
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- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 claims 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims 1
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- 241000238557 Decapoda Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000012356 Product development Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000003975 animal breeding Methods 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940116229 borneol Drugs 0.000 description 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 description 1
- 239000011449 brick Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- RDFLLVCQYHQOBU-ZOTFFYTFSA-O cyanin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C(=[O+]C1=CC(O)=C2)C=3C=C(O)C(O)=CC=3)=CC1=C2O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 RDFLLVCQYHQOBU-ZOTFFYTFSA-O 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000013022 formulation composition Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940119170 jojoba wax Drugs 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000000668 oral spray Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- UWJJYHHHVWZFEP-UHFFFAOYSA-N pentane-1,1-diol Chemical compound CCCCC(O)O UWJJYHHHVWZFEP-UHFFFAOYSA-N 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- CASUWPDYGGAUQV-UHFFFAOYSA-M potassium;methanol;hydroxide Chemical compound [OH-].[K+].OC CASUWPDYGGAUQV-UHFFFAOYSA-M 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
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- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- -1 undecylenoyl phenylpropane amino acid Chemical class 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Images
Classifications
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Definitions
- the present invention relates to the technical field of hyaluronic acid, and in particular, to a hyaluronic acid composition with a permeation-promoting effect, a preparation method and an application thereof.
- the skin is the largest organ of the human body.
- the average adult skin surface area is about 1.6m 2 , and the total weight accounts for about 16% of the body weight.
- the skin is divided into three parts: epidermis, dermis and subcutaneous tissue from the outside and inside.
- the skin is not only decorative for human beings.
- Outerwear also has a strong protective effect.
- the brick wall structure of the epidermis allows the skin to block foreign substances from the skin, thereby protecting our human body.
- the active substances in skin care products must enter the target level of the skin to function. Therefore, in the field of skin care products, it is particularly important to promote the absorption of nutrients.
- formulators In the field of drug development, formulators often use propylene glycol, azone, menthol, borneol, etc. as penetration enhancers to promote the absorption of drugs to exert a local therapeutic effect, because drugs are only used when they are sick, and are generally For topical use, adverse reactions such as sensitivity and redness will not be considered more carefully.
- Cosmetics are preparations that are used every morning and night, so there is a special need for skin-safer penetration-enhancing ingredients.
- MB Brown European Academy of Dermatology and Venereology, 2005: 19, 308–3178 et al. used sodium hyaluronate as the drug matrix to compare with water, chondroitin sulfate and sodium carboxymethyl cellulose as the matrix and found that HA could significantly strengthen The distribution of diclofenac sodium in all layers of the skin, and the retention and localization of the drug in the epidermis, the concentration of HA in this experiment was 2.5%.
- CN202010407830.1 a kind of patent application of a composition containing hyaluronic acid and polyol and its application, the inventor discloses a composition of hyaluronic acid and polyol, which can improve the water-soluble amino acid composition. Transdermal absorption, so that it can enter the epidermis and dermis without the aid of equipment, provide impact, exert cosmetic effects, the composition is composed of high, low and oligomeric hyaluronic acid or its salts, and polyols Antioxidant-like composition, the composition is relatively complex.
- the present invention Based on the actual needs of the current skin care product development and the problems existing in the current penetration enhancing system, the present invention combines hydrolyzed hyaluronic acid or its salt, hyaluronic acid or its salt, and acetylated hyaluronic acid or its salt, and applies it to the formula , the transdermal absorption rate of the target active substance can be significantly improved.
- a hyaluronic acid composition comprising:
- Hyaluronic acid or its salts
- the hyaluronic acid composition is composed of hyaluronic acid or its salt, acetylated hyaluronic acid or its salt, and hydrolyzed hyaluronic acid or its salt.
- the hyaluronic acid or its salt is 20-60%, preferably 25-55%, more preferably 25-40%;
- the acetylated hyaluronic acid or its salt is 10-50%, preferably 15-45%, more preferably 20-35%;
- the hydrolyzed hyaluronic acid or its salt is 30-70%, preferably 30-60%, more preferably 40-55%.
- the molecular weight of the hyaluronic acid or its salt is 100k-500kDa, preferably 150k-300kDa, more preferably 210k-300kDa;
- the molecular weight of the acetylated hyaluronic acid or its salt is 10k-100kDa, preferably 10k-50kDa, more preferably 20k-30kDa; and
- the molecular weight of the hydrolyzed hyaluronic acid or its salt is 0.8k-20kDa, preferably 3k-15kDa, more preferably 3k-10kDa.
- composition according to any one of items 1 to 4, wherein the acetyl group content of the acetylated hyaluronic acid or a salt thereof is 20 to 30 wt%.
- a method of preparing a hyaluronic acid composition comprising the steps of:
- the obtained solution is obtained by spray-drying.
- the hyaluronic acid or its salt is 20-60%, preferably 25-55%, more preferably 25-40%;
- the acetylated hyaluronic acid or its salt is 10-50%, preferably 15-45%, more preferably 20-35%;
- the hydrolyzed hyaluronic acid or its salt is 30-70%, preferably 30-60%, more preferably 40-55%.
- the molecular weight of the hyaluronic acid or its salt is 100k-500kDa, preferably 150k-300kDa, more preferably 210k-300kDa;
- the molecular weight of the acetylated hyaluronic acid or its salt is 10k-100kDa, preferably 10k-50kDa, more preferably 20k-30kDa; and
- the molecular weight of the hydrolyzed hyaluronic acid or its salt is 0.8k-20kDa, preferably 3k-15kDa, more preferably 3k-10kDa.
- compositions for promoting absorption of an active ingredient wherein the composition comprises an active ingredient and the hyaluronic acid composition of any one of items 1-5 or the hyaluronic acid composition of any one of items 6-11
- the hyaluronic acid composition prepared by the preparation method.
- composition according to item 12 wherein the water-soluble active ingredients are tranexamic acid, niacinamide, vitamin C, ergothioneine, small peptides containing 2-10 amino acids, aminobutyric acid, deoxygenated Ribonucleic acid, Boseine or Ectoine, the oil-soluble active ingredients are astaxanthin, salicylic acid, ferulic acid, phenethyl resorcinol, resveratrol, undecylenoyl benzene Alanine or ethylbisiminomethylguaiacol manganese chloride.
- the water-soluble active ingredients are tranexamic acid, niacinamide, vitamin C, ergothioneine, small peptides containing 2-10 amino acids, aminobutyric acid, deoxygenated Ribonucleic acid, Boseine or Ectoine
- the oil-soluble active ingredients are astaxanthin, salicylic acid, ferulic acid, pheneth
- composition according to item 12 or 13, wherein the mass ratio of the active ingredient to the hyaluronic acid composition is 1:5-5:1, preferably 1:4-4:1.
- the active ingredient is a water-soluble active ingredient and/or an oil-soluble active ingredient.
- the water-soluble active ingredients are tranexamic acid, niacinamide, vitamin C, ergothioneine, small peptides containing 2-10 amino acids, aminobutyric acid, deoxyribose Nucleic acid, boseine or ectoine
- the oil-soluble active ingredients are astaxanthin, salicylic acid, ferulic acid, phenethyl resorcinol, resveratrol, undecylenoyl phenylpropane amino acid or ethylbisiminomethylguaiacol manganese chloride.
- An article of manufacture comprising the composition of any of items 12-14.
- the hyaluronic acid composition according to any one of items 1-5 or the hyaluronic acid composition prepared by the preparation method according to any one of items 6-11 in the field of products, preferably, The hyaluronic acid composition is 0.1-2%, preferably 0.5-1.5%, based on the weight percentage in the product.
- composition of the hyaluronic acid or its salt with a permeation-promoting effect of the present invention which is added in a small amount, can effectively promote the absorption of other active ingredients in the formula, and achieve a synergistic effect.
- composition of the hyaluronic acid or its salt with the effect of promoting penetration of the present invention has small particle size, uniformity, fast dissolution speed, excellent absorption speed in the product, and is better than simple mixing in improving skin hydration. Way processed hyaluronic acid.
- FIG. 1 is a linear equation of tranexamic acid of Application Verification Example 1.
- Example 2 is a schematic diagram of the cumulative permeation amount per unit area of tranexamic acid in the in vitro permeation experiment using the hyaluronic acid composition obtained in Example 6 and the reference substance in Application Verification Example 1.
- FIG. 3 is a schematic diagram of the amount of tranexamic acid stored in the skin at different times during the experiment using the hyaluronic acid composition obtained in Example 6 in Application Verification Example 1.
- FIG. 3 is a schematic diagram of the amount of tranexamic acid stored in the skin at different times during the experiment using the hyaluronic acid composition obtained in Example 6 in Application Verification Example 1.
- FIG. 4 is a linear equation of astaxanthin in Application Verification Example 2.
- the present invention provides a hyaluronic acid composition
- a hyaluronic acid composition comprising hyaluronic acid or its salt, acetylated hyaluronic acid or its salt, and hydrolyzed hyaluronic acid or its salt.
- the acetylated hyaluronic acid or its salt is obtained by acetylation of hyaluronic acid or its salt, and the introduction of an acetyl group makes the acetylated hyaluronic acid or its salt lipophilic.
- the hydrolyzed hyaluronic acid or its salt is an oligomeric hyaluronic acid or its salt produced by using an enzymatic degradation technology, and has a smaller molecular weight and is more easily absorbed into the epidermis and the dermis.
- the hyaluronic acid or its salt is 20-60%, preferably 25-55%, It is further preferably 25-40%; the acetylated hyaluronic acid or its salt is 10-50%, preferably 15-45%, more preferably 20-35%; and the hydrolyzed hyaluronic acid or its salt is 30-70%, preferably 30-60%, more preferably 40-55%.
- the content of the hyaluronic acid or its salt can be 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, or any range in between;
- the acetylated hyaluronic acid or its salt can be 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% or any range therebetween;
- the hydrolyzed hyaluronic acid or its salt may be 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or any range therebetween.
- the molecular weight of the hyaluronic acid or its salt is 100k-500kDa, preferably 150k-300kDa, more preferably 210k-300kDa; the acetylated hyaluronic acid or The molecular weight of its salt is 10k-100kDa, preferably 10k-50kDa, more preferably 20k-30kDa; and the molecular weight of the hydrolyzed hyaluronic acid or its salt is 0.8k-20kDa, preferably 3k-15kDa, more preferably 3k -10kDa.
- the molecular weight of the hyaluronic acid or its salt may be 100kDa, 110kDa, 120kDa, 130kDa, 140kDa, 150kDa, 160kDa, 170kDa, 180kDa, 190kDa, 200kDa, 210kDa, 220kDa, 230kDa, 240kDa, 250kDa, 260kDa, 270kDa, 280kDa, 290kDa, 300kDa, 350kDa, 400kDa, 450kDa, 500kDa, or any range therebetween;
- the molecular weight of the acetylated hyaluronic acid or its salt can be 10kDa, 20kDa, 30kDa, 40kDa, 50kDa, 60kDa, 70kDa, 80kDa, 90kDa, 100kDa or any range therebetween;
- the molecular weight of the hydrolyzed hyaluronic acid or its salt can be 0.8kDa, 0.9kDa, 1kDa, 2kDa, 3kDa, 4kDa, 5kDa, 6kDa, 7kDa, 8kDa, 9kDa, 10kDa, 11kDa, 12kDa, 13kDa, 14kDa, 15kDa, 16kDa , 17kDa, 18kDa, 19kDa, 20kDa, or any range in between.
- the acetyl group content of the acetylated hyaluronic acid or its salt is 20-30 wt%.
- the acetyl group content for acetylated hyaluronic acid or a salt thereof may be, for example, 20wt%, 21wt%, 22wt%, 23wt%, 24wt%, 25wt%, 26wt%, 27wt%, 28wt%, 29wt%, 30wt% or any range in between.
- the hyaluronic acid composition is composed of hyaluronic acid or its salt, acetylated hyaluronic acid or its salt, and hydrolyzed hyaluronic acid or its salt.
- the hyaluronate or acetylated hyaluronate or hydrolyzed hyaluronate refers to metal ion salts, such as sodium salts, potassium salts, calcium salts, zinc salts, etc., usually sodium salts.
- the hyaluronic acid composition comprises hyaluronic acid or its salt; acetylated hyaluronic acid or its salt; and hydrolyzed hyaluronic acid or its salt,
- the hyaluronic acid or its salt is 20-60%, preferably 25-55%, more preferably 25-40%;
- the acetylated hyaluronic acid or its salt is 10-50%, preferably 15-45%, more preferably 20-35%;
- the hydrolyzed hyaluronic acid or its salt is 30-70%, preferably 30-60%, more preferably 40-55%.
- the hyaluronic acid composition comprises hyaluronic acid or its salt; acetylated hyaluronic acid or its salt; and hydrolyzed hyaluronic acid or its salt,
- the hyaluronic acid or its salt is 20-60%, preferably 25-55%, more preferably 25-40%;
- the acetylated hyaluronic acid or its salt is 10-50%, preferably 15-45%, more preferably 20-35%;
- the hydrolyzed hyaluronic acid or its salt is 30-70%, preferably 30-60%, more preferably 40-55%;
- the molecular weight of the hyaluronic acid or its salt is 100k-500kDa, preferably 150k-300kDa, more preferably 210k-300kDa;
- the molecular weight of the acetylated hyaluronic acid or its salt is 10k-100kDa, preferably 10k-50kDa, more preferably 20k-30kDa; and
- the molecular weight of the hydrolyzed hyaluronic acid or its salt is 0.8k-20kDa, preferably 3k-15kDa, more preferably 3k-10kDa.
- the hyaluronic acid composition comprises hyaluronic acid or its salt; acetylated hyaluronic acid or its salt; and hydrolyzed hyaluronic acid or its salt,
- the hyaluronic acid or its salt is 20-60%, preferably 25-55%, more preferably 25-40%;
- the acetylated hyaluronic acid or its salt is 10-50%, preferably 15-45%, more preferably 20-35%;
- the hydrolyzed hyaluronic acid or its salt is 30-70%, preferably 30-60%, more preferably 40-55%;
- the molecular weight of the hyaluronic acid or its salt is 100k-500kDa, preferably 150k-300kDa, more preferably 210k-300kDa;
- the molecular weight of the acetylated hyaluronic acid or its salt is 10k-100kDa, preferably 10k-50kDa, more preferably 20k-30kDa; and
- the molecular weight of the hydrolyzed hyaluronic acid or its salt is 0.8k-20kDa, preferably 3k-15kDa, more preferably 3k-10kDa, and the acetyl group content of the acetylated hyaluronic acid or its salt is 20-30wt%.
- hyaluronic acid or its salt is equivalent to a very small network structure, which is distributed on the surface layer of the skin, and acetylated hyaluronic acid or its salt has an acetylated Base, with lipophilicity, can be skin friendly, form channels, hydrolyze hyaluronic acid or its salts.
- the channels formed by acetylated hyaluronic acid or its salts can quickly penetrate into the skin layer, hydrolyze hyaluronic acid or its salts
- the skin barrier can be quickly opened, and nutrients, hydrolyzed hyaluronic acid or its salts, and nutrients bound by hyaluronic acid or its salts can enter the skin, promoting the activation of active molecules.
- Absorption such as promoting the absorption of oil-soluble active ingredients in skin care products or the absorption of water-soluble active ingredients, and promoting the absorption of other active ingredients in disinfection products, medicines, dressings or gel medical devices.
- the invention provides a method for preparing a hyaluronic acid composition, which comprises the following steps:
- the obtained solution is obtained by spray-drying.
- the feed temperature of spray drying is 120-150°C
- the discharge temperature is 80-100°C
- the atomization frequency is 30-50 Hz.
- the feed temperature for spray drying can be 120°C, 125°C, 130°C, 135°C, 140°C, 145°C, 150°C, or any range therebetween;
- the discharge rate can be, for example, 80°C, 85°C, 90°C, 95°C, 100°C, or any range therebetween.
- the atomization rate can be, for example, 30 Hz, 35 Hz, 40 Hz, 45 Hz, 50 Hz, or any range in between.
- the hyaluronic acid composition obtained after spray drying is fine particles that can pass through 100-200 meshes.
- the present invention provides a composition for promoting the absorption of an active ingredient, wherein the composition comprises an active ingredient and the above-mentioned hyaluronic acid composition or the hyaluronic acid composition prepared by the above-mentioned preparation method.
- the active ingredient may be an active ingredient known to those skilled in the art, such as an active ingredient in the field of skin care products, an active ingredient in a medicine, an active ingredient in a disinfection product, an active ingredient in a dressing, or an active ingredient in a gel medical device. Active ingredient.
- the gel medical devices refer to medical devices such as oral and nasal sprays and repair gels.
- the active ingredient is a water-soluble active ingredient and/or an oil-soluble active ingredient.
- the water-soluble active ingredient refers to a water-soluble active ingredient, which can be any water-soluble active ingredient known to those skilled in the art that can be used in skin care products or gel medical devices, such as tranexamic acid , niacinamide, vitamin C, ergothioneine, small molecule peptides containing 2-10 amino acids, aminobutyric acid, deoxyribose nucleic acid, boson or ectoine.
- the oil-soluble active ingredient refers to a water-insoluble active ingredient, which can be any oil-soluble active ingredient known to those skilled in the art that can be used in skin care products or gel medical devices, such as astaxanthin , salicylic acid, ferulic acid, phenethyl resorcinol, resveratrol, undecylenoyl phenylalanine or ethylbisiminomethylguaiacol manganese chloride.
- the mass ratio of the active ingredient to the hyaluronic acid composition is 1:5-5:1, preferably 1:4-4:1.
- the mass ratio of the active ingredient to the hyaluronic acid composition is 1:5, 1:4, 1:3, 1:2, 1:1, 2: 1, 3:1, 4:1, 5:1, or any range in between.
- the present invention provides the use of the above-mentioned hyaluronic acid composition or the hyaluronic acid composition prepared by the above-mentioned preparation method in improving the absorption of active ingredients, preferably, the active ingredients are water-soluble active ingredients and /or oil-soluble active ingredients.
- the water-soluble active ingredients are tranexamic acid, niacinamide, vitamin C, ergothioneine, small molecule peptides containing 2-10 amino acids, aminobutyric acid, deoxygenated Ribonucleic acid, Boseine or Ectoine
- the oil-soluble active ingredients are astaxanthin, salicylic acid, ferulic acid, phenethyl resorcinol, resveratrol, undecylenoyl benzene Alanine or ethylbisiminomethylguaiacol manganese chloride.
- the present invention provides an article comprising the composition described above.
- the hyaluronic acid composition is 0.1-2%, preferably 0.5-1.5%, in terms of mass percentage in the product.
- the hyaluronic acid composition can be 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1 %, 2%, or any range in between.
- the product is a skin care product, a disinfection product, a medicine or dressing, and a gel medical device.
- the skin care product is a toner, essence, cream, facial mask, lotion or other body care products.
- the product further includes other auxiliary materials, and the auxiliary materials are any known auxiliary materials in the art.
- the auxiliary materials of the skin care product can be butanediol, pentanediol, Glycerin, caprylic capric triglyceride, jojoba oil, hydrogenated lecithin, xanthan gum, carbomer, triethanolamine, poloxamer, tranexamic acid, astaxanthin, ethyl paraben, etc.
- the present invention provides the application of the above-mentioned hyaluronic acid composition or the hyaluronic acid composition prepared by the above-mentioned preparation method in the field of products.
- the hyaluronic acid composition is 0.1-2%, preferably 0.5-1.5%.
- the product is a skin care product, a disinfection product, a medicine or dressing, and a gel medical device.
- hyaluronic acid composition in the present invention can promote the absorption of active ingredients in products such as skin care products, medicines, disinfection products, dressings or gel medical devices, thereby improving the transdermal absorption rate of active ingredients.
- the present invention generally and/or specifically describes the materials and test methods used in the test.
- % represents wt%, that is, weight percentage.
- the reagents or instruments used without the manufacturer's indication are all conventional reagent products that can be obtained from the market.
- aqueous solution is treated by spray drying.
- the feeding temperature was set to 125°C
- the discharge temperature was 90°C
- the atomizer frequency was 40 Hz to obtain uniform and fine powder.
- the aqueous solution is treated by spray drying.
- the feeding temperature was set to 140°C
- the discharge temperature was 80°C
- the atomizer frequency was 30 Hz to obtain uniform fine powder.
- aqueous solution is treated by spray drying.
- the feeding temperature was set to 150°C
- the discharge temperature was 80°C
- the atomizer frequency was 50 Hz to obtain uniform fine powder.
- aqueous solution is treated by spray drying.
- the feeding temperature was set to 120°C
- the discharge temperature was 100°C
- the atomizer frequency was 30 Hz to obtain uniform fine powder.
- the dissolving properties of the compositions obtained in Examples 1-13 are better, and the dissolving time is less than 25min, while the dissolving time of the compositions obtained in Comparative Examples 1-4 is longer, more than 29min,
- the composition of the present invention has better solubility.
- Example 1 90%
- Example 2 99%
- Example 3 100%
- Example 4 99%
- Example 5 99%
- Example 6 100%
- Example 7 98%
- Example 8 95%
- Example 9 95%
- Example 10 94%
- Example 11 89%
- Example 12 92%
- Example 13 85% Comparative Example 1 65% Comparative Example 2 83% Comparative Example 3 79% Comparative Example 4 80%
- the compositions obtained in Examples 1-13 were sieved through a 200-mesh sieve, and the pass rate was above 85%, indicating that the particle size of the obtained composition was small and the particle size was relatively uniform.
- the pass rate of the comparative example is below 83%, which shows that the particle size of the composition of the present invention is small and the particle size is relatively uniform.
- the abdominal skin of SD rats (the rats were purchased from Qinglongshan Animal Breeding Farm, Jiangning District, Nanjing City, and the abdominal skin was stripped by the laboratory) was taken, and after removing the tissues such as fat, muscle, and mucous membrane, it was sandwiched in the middle of the Franz diffusion cell. °C water bath, the control group supply pool was given 1ml of the reference solution, and the sample group supply pool was given 1ml of the same concentration of the verification formula.
- the receiving tank was filled with an appropriate amount of normal saline and stirred at 400 r/min.
- Cn and Ci are the drug mass concentration ( ⁇ g/ml) measured at the n and i sampling points, respectively, V and V0 are the receiving tank volume and sampling volume (ml), respectively, and A is the permeation area (cm 2 ).
- the cumulative permeation of the control formula tranexamic acid for 24h is (24.3 ⁇ 14.9) ⁇ g/cm 2
- the cumulative permeation of the experimental formula tranexamic acid for 24h is (92.2 ⁇ 23.3) ⁇ g/cm 2 , about It is 4 times of the control formula, and the difference between groups is very obvious (t test, P ⁇ 0.01). Since the only difference between the two formulations is the hyaluronic acid composition, it is indicated that when the hyaluronic acid composition in Example 6 is added to the formulation as a carrier for transdermal administration, the transdermal absorption of tranexamic acid can be significantly promoted.
- the abdominal skin of SD rats was taken, after removing fat, muscle, mucosa and other tissues, it was sandwiched in the middle of Franz diffusion cell, and water bathed at 32 °C.
- the control group was given 1ml of the reference solution in the supply pool, and the sample group was given 1ml of the same concentration of the verification formula.
- the receiving tank was filled with an appropriate amount of normal saline and stirred at 400 r/min.
- the skin retention of tranexamic acid in the verification formula group reached the highest value of 153.12 ⁇ g/cm 2 in 2 hours, which was higher than that in the control experimental group, indicating that after adding the hyaluronic acid composition in Example 6, the retention rate of Clear acid can be quickly stored in the epidermis layer of the skin, which is beneficial to the transdermal absorption in the following time.
- Skin hydration refers to the ability of keratin or its degradation products in the outer layer of the skin to combine with water, and the degree of hydration refers to the water content of the stratum corneum. Hydration will increase the water content of the stratum corneum of the skin, so that the tissue becomes soft, the keratinocytes are filled, the water content of the intercellular space increases, and the gap becomes larger, which is conducive to the percutaneous penetration of active ingredients.
- Volunteers first need to wash the inner forearms of both hands with clean water, press the moisture test probe vertically on the surface of the skin to be tested after 30 minutes, adjust the pressing force according to the screen display of the instrument until the measurement result is displayed, then apply the sample to be tested, and then repeat it after 30 minutes.
- the degree of hydration was measured, and the rate of increase in the degree of hydration was calculated according to the formula.
- H is the hydration degree increase rate
- H1 is the hydration degree measured after applying the sample
- H0 is the hydration degree measured before the sample is applied.
- the calculated hydration degree increase rate was 78.61%.
- the cumulative penetration amount and the skin retention amount are both high, and the hydration degree improvement rate is high. Also high, because the hyaluronic acid or its salt in the hyaluronic acid composition of the examples has a good moisturizing effect, and the acetylated hyaluronic acid or its salt can also promote skin hydration, thereby softening the tissue, keratin The cells are filled, the water content of the intercellular space is increased, the skin barrier is opened, and the free nutrients and the nutrients bound by hydrolyzed hyaluronic acid or its salts and hyaluronic acid or its salts enter the skin, thereby promoting active absorption, It is illustrated that the hyaluronic acid composition described in the examples can promote the rapid penetration of tranexamic acid through the skin, and is stored in the epidermis, which is beneficial to the transdermal absorption
- Verified formula (percentage %) Control formula (percentage %) Caprylic Capric Triglyceride 3 3 Astaxanthin 0.1 0.1 Hyaluronic acid composition of Example 6 0.4 0 Hydrogenated Lecithin 0.5 0.5 Xanthan Gum 0.1 0.1 Butanediol 4 4 glycerin 2 2 carbomer 0.1 0.1 Triethanolamine 0.07 0.07 purified water to 100 to 100
- HEC hydroxyethyl cellulose
- the abdominal skin of SD rats was removed, and the tissues such as fat, muscle and mucous membrane were removed, and then sandwiched in the middle of Franz diffusion cell in a water bath at 32°C.
- the supply pool of the control group was given 1ml of the two reference solutions respectively, the supply pool of the sample group was given 1ml of the same concentration of the sample, and the receiving pool was filled with an appropriate amount of 1% Tween 80 solution and stirred.
- the tissues were taken out at 2.0h, 4.0h, 6.0h, 12.0h, and 24.0h, respectively, and the surface residues were washed with normal saline for 5 times, blotted dry with filter paper, cut off the skin that penetrated effectively, and 4ml of solvent (methanol: dichloromethane 3 : 1), pulverized with a tissue pulverizer for 2 min, ultrasonically extracted for 30 min, added 1 ml of 1% KOH methanol solution, shaken well, reacted at 30 °C for 30 min, centrifuged at 5000 r/min for 5 min at 4 °C, and filtered with a 0.22 ⁇ m membrane to obtain the data.
- solvent methanol: dichloromethane 3 : 1
- the 24h full face retention of the control formula group and the verification formula group were 0.011 ⁇ g/cm 2 and 0.038 ⁇ g/cm 2 respectively, and there was a significant difference between the two groups of retention, the only difference between the two groups. It is because the content of hyaluronic acid composition is different (the verification formula contains 0.4% hyaluronic acid composition, and the control formula does not contain hyaluronic acid), so it is considered that the hyaluronic acid composition of Example 6 is in the transdermal absorption of astaxanthin played a key role.
- Skin hydration refers to the ability of the outer layer of keratin or its degradation products to combine with water, and the degree of hydration refers to the water content of the stratum corneum. Hydration will increase the water content of the stratum corneum of the skin, so that the tissue becomes soft, the keratinocytes are filled, the water content of the intercellular space increases, and the gap becomes larger, which is conducive to the percutaneous penetration of active ingredients.
- Volunteers first need to wash the inner forearms of both hands with clean water, press the moisture test probe vertically on the surface of the skin to be tested after 30 minutes, adjust the pressing force according to the screen display of the instrument until the measurement result is displayed, then apply the sample to be tested, and then repeat it after 30 minutes.
- the degree of hydration was measured, and the rate of increase in the degree of hydration was calculated according to the formula.
- H is the hydration degree increase rate
- H1 is the hydration degree measured after applying the sample
- H0 is the hydration degree measured before the sample is applied.
- the obtained hydration degree improvement rate was 86.44%.
- Example 1 0.028 32.87
- Example 2 0.051 90.33
- Example 3 0.049 89.34
- Example 4 0.058 90.37
- Example 5 0.042 88.47
- Example 7 0.034 65.22
- Example 8 0.032 68.18
- Example 9 0.033 59.09
- Example 10 0.034 46.67
- Example 11 0.025 38.62
- Example 12 0.023 31.10
- Example 13 0.018 30.03
- Comparative Example 1 0.012 27.14
- Comparative Example 2 0.016 23.33
- the hyaluronic acid composition described in the example has a significant difference in skin retention within 24h compared with that of the comparative example, indicating that the hyaluronic acid composition described in the example can promote shrimp Transdermal absorption of cyanin; in addition, there is also a significant difference in the rate of hydration improvement compared with the comparative example.
- hydration represents the water content of the stratum corneum
- hydration will increase the water content of the stratum corneum of the skin, thereby tissue
- the keratinocytes become soft, the keratinocytes are filled, the water content of the intercellular space increases, and the space becomes larger, which is beneficial to the percutaneous penetration of the active ingredient, which further illustrates that the hyaluronic acid composition of the present invention can promote the absorption of the active ingredient.
- the present invention adopts the hyaluronic acid composition, hyaluronic acid or its salt is equivalent to a very small network structure, which is distributed on the surface layer of the skin, and acetylated hyaluronic acid or its salt has an acetyl group.
- the hyaluronic acid composition can increase the degree of hydration, thereby softening the tissue, filling the keratinocytes, increasing the water content of the intercellular space, and making the space larger, which is beneficial to the percutaneous penetration of the active ingredient.
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Abstract
Description
原料名称 | 纯度 | 生产厂家 |
透明质酸钠 | >92% | 华熙生物科技股份有限公司 |
乙酰化透明质酸钠 | >92% | 华熙生物科技股份有限公司 |
水解透明质酸钠 | >92% | 华熙生物科技股份有限公司 |
传明酸 | >99% | 市售 |
虾青素 | >90% | 市售 |
溶解性能(min) | |
实施例1 | 18 |
实施例2 | 14 |
实施例3 | 12 |
实施例4 | 11 |
实施例5 | 13 |
实施例6 | 12 |
实施例7 | 17 |
实施例8 | 15 |
实施例9 | 16 |
实施例10 | 16 |
实施例11 | 21 |
实施例12 | 20 |
实施例13 | 25 |
对比例1 | 60 |
对比例2 | 38 |
对比例3 | 29 |
对比例4 | 46 |
通过率 | |
实施例1 | 90% |
实施例2 | 99% |
实施例3 | 100% |
实施例4 | 99% |
实施例5 | 99% |
实施例6 | 100% |
实施例7 | 98% |
实施例8 | 95% |
实施例9 | 95% |
实施例10 | 94% |
实施例11 | 89% |
实施例12 | 92% |
实施例13 | 85% |
对比例1 | 65% |
对比例2 | 83% |
对比例3 | 79% |
对比例4 | 80% |
吸收度(s) | |
实施例1 | 21 |
实施例2 | 16 |
实施例3 | 15 |
实施例4 | 12 |
实施例5 | 13 |
实施例6 | 11 |
实施例7 | 18 |
实施例8 | 17 |
实施例9 | 19 |
实施例10 | 19 |
实施例11 | 23 |
实施例12 | 21 |
实施例13 | 24 |
对比例1 | 40 |
对比例2 | 28 |
对比例3 | 31 |
对比例4 | 26 |
原料 | 验证配方(百分含量%) | 对照配方(百分含量%) |
辛酸癸酸甘油三酯 | 3 | 3 |
实施例6的透明质酸组合物 | 1.0 | 0 |
丁二醇 | 4 | 4 |
甘油 | 2 | 2 |
传明酸 | 2 | 2 |
卡波姆 | 0.15 | 0.15 |
泊洛沙姆 | 0.4 | 0.4 |
羟苯乙酯 | 0.1 | 0.1 |
三乙醇胺 | 0.07 | 0.07 |
纯化水 | 至100 | 至100 |
验证配方(百分含量%) | 对照配方(百分含量%) | |
辛酸癸酸甘油三酯 | 3 | 3 |
虾青素 | 0.1 | 0.1 |
实施例6的透明质酸组合物 | 0.4 | 0 |
氢化卵磷脂 | 0.5 | 0.5 |
黄原胶 | 0.1 | 0.1 |
丁二醇 | 4 | 4 |
甘油 | 2 | 2 |
卡波姆 | 0.1 | 0.1 |
三乙醇胺 | 0.07 | 0.07 |
纯化水 | 至100 | 至100 |
时间/h | 2 | 4 | 6 | 12 | 24 |
肌底液储留量/μg/cm 2 | 0.026 | 0.023 | 0.026 | 0.026 | 0.038 |
对照组储留量/μg/cm 2 | - | - | - | - | 0.011 |
皮肤储留量(μg/cm 2)(24h) | 水合度提高率(%) | |
实施例1 | 0.028 | 32.87 |
实施例2 | 0.051 | 90.33 |
实施例3 | 0.049 | 89.34 |
实施例4 | 0.058 | 90.37 |
实施例5 | 0.042 | 88.47 |
实施例7 | 0.034 | 65.22 |
实施例8 | 0.032 | 68.18 |
实施例9 | 0.033 | 59.09 |
实施例10 | 0.034 | 46.67 |
实施例11 | 0.025 | 38.62 |
实施例12 | 0.023 | 31.10 |
实施例13 | 0.018 | 30.03 |
对比例1 | 0.012 | 27.14 |
对比例2 | 0.016 | 23.33 |
对比例3 | 0.010 | 18.38 |
对比例4 | 0.012 | 18.75 |
对照配方 | 0.011 | 35.25 |
Claims (22)
- 一种透明质酸组合物,其包括:透明质酸或其盐;乙酰化透明质酸或其盐;以及水解透明质酸或其盐。
- 根据权利要求1所述的透明质酸组合物,其中,所述透明质酸组合物由透明质酸或其盐、乙酰化透明质酸或其盐和水解透明质酸或其盐组成。
- 根据权利要求1或2所述的透明质酸组合物,其中,以在透明质酸组合物中所占的重量百分比计,所述透明质酸或其盐为20-60%,优选为25-55%,进一步优选为25-40%;所述乙酰化透明质酸或其盐为10-50%,优选为15-45%,进一步优选为20-35%;以及所述水解透明质酸或其盐为30-70%,优选为30-60%,进一步优选为40-55%。
- 根据权利要求1-3中任一项所述的透明质酸组合物,其中,所述透明质酸或其盐的分子量为100k-500kDa,优选为150k-300kDa,进一步优选为210k-300kDa;所述乙酰化透明质酸或其盐的分子量为10k-100kDa,优选为10k-50kDa,进一步优选为20k-30kDa;以及所述水解透明质酸或其盐的分子量为0.8k-20kDa,优选为3k-15kDa,进一步优选为3k-10kDa。
- 根据权利要求1-4中任一项所述的组合物,其中,所述乙酰化透明质酸或其盐的乙酰基含量为20-30wt%。
- 一种制备透明质酸组合物的方法,其包括下述步骤:将透明质酸或其盐、乙酰化透明质酸或其盐和水解透明质酸或其盐溶解得到溶液;将所得到的溶液进行喷雾干燥处理得到。
- 根据权利要求6所述的方法,其中,以在溶液中所占的质量百分比计, 所述透明质酸或其盐、乙酰化透明质酸或其盐和水解透明质酸或其盐的总和为1-10%。
- 根据权利要求6或7所述的方法,其中,喷雾干燥的进料温度为120-150℃,出料温度为80-100℃,优选的,雾化频率为30-50Hz。
- 根据权利要求6-8中任一项所述的方法,其中,以在透明质酸组合物中所占的重量百分比计,所述透明质酸或其盐为20-60%,优选为25-55%,进一步优选为25-40%;所述乙酰化透明质酸或其盐为10-50%,优选为15-45%,进一步优选为20-35%;以及所述水解透明质酸或其盐为30-70%,优选为30-60%,进一步优选为40-55%。
- 根据权利要求6-9中任一项所述的方法,其中,所述透明质酸或其盐的分子量为100k-500kDa,优选为150k-300kDa,进一步优选为210k-300kDa;所述乙酰化透明质酸或其盐的分子量为10k-100kDa,优选为10k-50kDa,进一步优选为20k-30kDa;以及所述水解透明质酸或其盐的分子量为0.8k-20kDa,优选为3k-15kDa,进一步优选为3k-10kDa。
- 根据权利要求6-10中任一项所述的方法,其中,所述乙酰透明质酸或其盐的乙酰基含量为20%-30%。
- 一种促进活性成分吸收的组合物,其中,所述组合物包含活性成分以及权利要求1-5中任一项所述的透明质酸组合物或者权利要求6-11中任一项所述的制备方法制备得到的透明质酸组合物。
- 根据权利要求12所述的组合物,其中,所述活性成分为水溶性活性成分和/或油溶性活性成分,优选的,所述水溶性活性成分为传明酸、烟酰胺、维生素C、麦角硫因、含2-10个氨基酸的小分子肽、氨基丁酸、脱氧核糖核酸、玻色因或依克多因,所述油溶性活性成分为虾青素、水杨酸、阿魏酸、苯乙基间苯二酚、白藜芦醇、十一碳烯酰基苯丙氨酸或乙基双亚氨基甲基愈创木酚锰氯化物。
- 根据权利要求12或13所述的组合物,其中,所述活性成分与所述 透明质酸组合物的质量比为1:5-5:1,优选为1:4-4:1。
- 权利要求1-5中任一项所述的透明质酸组合物或者权利要求6-11中任一项所述的制备方法制备得到的透明质酸组合物在改善活性成分吸收中的用途,优选的,所述活性成分为水溶性活性成分和/或油溶性活性成分。
- 根据权利要求15所述的用途,其中,所述水溶性活性成分为传明酸、烟酰胺、维生素C、麦角硫因、含2-10个氨基酸的小分子肽、氨基丁酸、脱氧核糖核酸、玻色因或依克多因,所述油溶性活性成分为虾青素、水杨酸、阿魏酸、苯乙基间苯二酚、白藜芦醇、十一碳烯酰基苯丙氨酸或乙基双亚氨基甲基愈创木酚锰氯化物。
- 一种制品,其包括权利要求12-14中任一项所述的组合物。
- 根据权利要求17所述的制品,其中,以在制品中所占的质量百分比计,所述透明质酸组合物为0.1-2%,优选为0.5-1.5%。
- 根据权利要求17或18所述的制品,其中,所述制品为护肤品、消毒产品、药品或敷料、凝胶类医疗器械。
- 根据权利要求19所述的制品,其中,所述护肤品为爽肤水、精华、膏霜、面膜或乳液。
- 权利要求1-5中任一项所述的透明质酸组合物或者权利要求6-11中任一项所述的制备方法制备得到的透明质酸组合物在制品领域中的应用,优选的,以在制品中所占的重量百分比计,所述透明质酸组合物为0.1-2%,优选为0.5-1.5%。
- 根据权利要求21所述的应用,其中,所述制品为护肤品、消毒产品、药品或敷料、凝胶类医疗器械。
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