CN113712851A - Penetrant based on tetrahydropiperine cyclodextrin inclusion compound and preparation method thereof - Google Patents
Penetrant based on tetrahydropiperine cyclodextrin inclusion compound and preparation method thereof Download PDFInfo
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- CN113712851A CN113712851A CN202111111398.2A CN202111111398A CN113712851A CN 113712851 A CN113712851 A CN 113712851A CN 202111111398 A CN202111111398 A CN 202111111398A CN 113712851 A CN113712851 A CN 113712851A
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- tetrahydropiperine
- cyclodextrin
- inclusion compound
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- cyclodextrin inclusion
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- 229920000858 Cyclodextrin Polymers 0.000 title claims abstract description 169
- APZYKUZPJCQGPP-UHFFFAOYSA-N Tetrahydropiperine Chemical compound C=1C=C2OCOC2=CC=1CCCCC(=O)N1CCCCC1 APZYKUZPJCQGPP-UHFFFAOYSA-N 0.000 title claims abstract description 146
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 title claims abstract description 121
- 150000001875 compounds Chemical class 0.000 title claims abstract description 81
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
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- 238000003756 stirring Methods 0.000 claims abstract description 37
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229920002101 Chitin Polymers 0.000 claims abstract description 26
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 claims abstract description 26
- 108010039918 Polylysine Proteins 0.000 claims abstract description 26
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims abstract description 24
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000010438 heat treatment Methods 0.000 claims abstract description 24
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims abstract description 24
- 229960000367 inositol Drugs 0.000 claims abstract description 24
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000001132 ultrasonic dispersion Methods 0.000 claims abstract description 8
- 238000001308 synthesis method Methods 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 9
- 238000001704 evaporation Methods 0.000 claims description 7
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- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 4
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims 1
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- 230000001737 promoting effect Effects 0.000 abstract description 6
- 239000000243 solution Substances 0.000 description 53
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 19
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Images
Classifications
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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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
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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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
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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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
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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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/736—Chitin; Chitosan; Derivatives thereof
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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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/738—Cyclodextrins
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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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/88—Polyamides
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- 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
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- 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
- A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Abstract
The invention relates to a penetrant based on a tetrahydropiperine cyclodextrin inclusion compound and a preparation method thereof. The penetrant comprises the following components: the high-efficiency synthesis method comprises the following steps of butanediol, glycerol, betaine, tetrahydropiperine cyclodextrin inclusion compound, hydrolyzed chitin, inositol and polylysine, wherein the tetrahydropiperine cyclodextrin inclusion compound comprises the tetrahydropiperine and cyclodextrin, and the weight ratio of the tetrahydropiperine to the cyclodextrin is 1 (1.0-10). The preparation method of the penetrant comprises the following steps: preparing a cyclodextrin solution, adding cyclodextrin into water, heating and stirring to fully dissolve the cyclodextrin to prepare a propylcyclodextrin solution; adding tetrahydropiperine into hydroxypropyl cyclodextrin water solution, heating and stirring at 40-60 ℃, and using ultrasonic dispersion to completely dissolve the tetrahydropiperine into the hydroxypropyl cyclodextrin solution; stirring for 2-10 hr to embed the tetrahydropiperine with hydroxypropyl cyclodextrin. The permeation promoting effect of the penetrant is better than that of the simple cyclodextrin embedded tetrahydropiperine.
Description
Technical Field
The invention belongs to the technical field of penetrants, and particularly relates to a penetrant based on a tetrahydropiperine cyclodextrin inclusion compound and a preparation method thereof.
Background
The skin is the largest organ of the human body and is also the most direct route of administration. In the medical field, dermal administration has many unique advantages over other routes of administration, including avoidance of first-pass effects, direct action on localized lesions, sustained release and controlled release rate of the drug, good patient compliance, etc. Dermal administration is also the most challenging of the non-invasive routes of administration and is also the most promising alternative to administration by injection to deliver the drug composition to the lesion. On the other hand, in the medical cosmetic field, skin has been the subject of human protection and beautification. With the aging, the skin becomes dry, dull, aged, and pigmented spots, and the most common way to combat these problems is to apply skin care products to the skin surface, wherein active ingredients with specific effects can moisturize and brighten the skin, reduce wrinkles, lighten pigmented spots, etc. after being absorbed by the skin. Therefore, research and application of percutaneous absorption of drugs and active ingredients are also becoming widespread.
However, the nature of skin is a biofilm barrier to the invasion of external pathogens, such as bacteria, viruses or exogenous allergens. Generally only a very small number of non-polar small molecules (molecular weight <500Da) can passively pass the skin barrier. Therefore, it is very challenging to deliver various drugs or active substances with different physicochemical properties, especially biomacromolecule drugs (polysaccharides, polypeptides, proteins, biological enzymes, nucleic acids, etc. with molecular weights of at least-104 Da, 105Da or even 106 Da) to the lesion site in the deep layer of the skin, and it is also a difficult point and a key point of research in the field of skin drug delivery.
At present, methods for promoting percutaneous absorption of drugs are roughly classified into chemical methods and physical methods. Chemical methods include the use of transdermal penetration enhancers, nanocarrier technologies (such as liposomes, microemulsions, polymeric nanoparticles, micelles, quantum dots, gold nanoparticles), and the like. The chemical permeation-promoting method has an insufficient significant permeation-promoting effect on biological macromolecules, and the application and industrialization of the chemical permeation-promoting method are greatly limited due to the problems of in vivo metabolism and cytotoxicity of many chemical permeation-promoting agents and nanoparticle systems. On the other hand, physical permeation-promoting techniques include iontophoresis, ultrasonic introduction, electroporation, and microneedle methods. Many of the physical permeation promoting technologies have obvious effects, but have high requirements on instruments and equipment, are not easy to carry, have high design and production costs, and can only be used for skin administration in small areas, so the application of the physical permeation promoting technologies is greatly limited.
Among the penetration enhancers, tetrahydropiperine is used in the field of medicine because of its natural origin and excellent penetration enhancing properties. However, the tetrahydropiperine has certain irritation to skin, has heat sensation during use, is poor in water solubility, has limitation in application in cosmetic formulations, and is not widely applied at present. Therefore, the development of a mild, non-irritating and penetration-promoting penetrant is urgently needed.
Disclosure of Invention
In order to achieve the purpose, the invention provides a penetrant based on a tetrahydropiperine cyclodextrin inclusion compound and a preparation method thereof. Moreover, under the action of molecular synergy, the permeation promoting effect of the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound is better than that of the penetrant based on the simple cyclodextrin-embedded tetrahydropiperine.
The technical scheme of the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound is as follows:
an osmotic agent based on tetrahydropiperine cyclodextrin inclusion compound comprises the following components: the high-efficiency synthesis method comprises the following steps of butanediol, glycerol, betaine, tetrahydropiperine cyclodextrin inclusion compound, hydrolyzed chitin, inositol and polylysine, wherein the tetrahydropiperine cyclodextrin inclusion compound comprises the tetrahydropiperine and cyclodextrin, and the weight ratio of the tetrahydropiperine to the cyclodextrin is 1 (1.0-10).
As a further improvement on the technical scheme, the hydroxypropyl cyclodextrin is hydroxypropyl-beta-cyclodextrin.
As a further improvement to the above technical scheme, in mass percent, the butanediol is 40-50%, the glycerol is 5-10%, the tetrahydropiperine cyclodextrin inclusion compound is 21.9-45.95%, the betaine is 5-10%, the hydrolyzed chitin is 2-4%, the inositol is 2-4%, and the polylysine is 0.05-0.1%.
The technical scheme of the preparation method of the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound is as follows:
a preparation method of a penetrant based on a tetrahydropiperine cyclodextrin inclusion compound comprises the following steps:
(1) preparing a cyclodextrin solution, adding cyclodextrin into water, heating and stirring to fully dissolve the cyclodextrin to prepare a propylcyclodextrin solution;
(2) adding tetrahydropiperine into cyclodextrin water solution, heating and stirring at 40-60 ℃, and simultaneously using ultrasonic dispersion to completely dissolve the tetrahydropiperine into the cyclodextrin solution;
(3) keeping the temperature unchanged, and continuously stirring for 2-10 hours to fully embed the tetrahydropiperine by the cyclodextrin;
(4) evaporating water to obtain tetrahydropiperine cyclodextrin clathrate;
(5) preparing tetrahydropiperine cyclodextrin inclusion compound solution, adding betaine, hydrolyzed chitin, inositol and polylysine into the tetrahydropiperine cyclodextrin inclusion compound solution, and heating and stirring at 40-60 deg.C to obtain uniform solution.
As a further improvement on the technical scheme, the hydroxypropyl cyclodextrin is hydroxypropyl-beta-cyclodextrin.
As a further improvement to the above technical scheme, in mass percent, the butanediol is 40-50%, the glycerol is 5-10%, the tetrahydropiperine cyclodextrin inclusion compound is 21.9-45.95%, the betaine is 5-10%, the hydrolyzed chitin is 2-4%, the inositol is 2-4%, and the polylysine is 0.05-0.1%.
The invention provides a penetrant based on a tetrahydropiperine cyclodextrin inclusion compound and a preparation method thereof, and compared with the prior art, the penetrant has the following advantages:
the novel penetrant based on the tetrahydropiperine cyclodextrin inclusion compound utilizes the hydrophobic cavity of cyclodextrin molecules to allow the tetrahydropiperine to enter the cavity to realize the embedding of the molecules, thereby greatly reducing the direct irritation of the tetrahydropiperine to skin and simultaneously enabling the tetrahydropiperine to be completely dissolved in water. The cosmetics containing the penetrant can be in the forms of aqua, emulsion, essence, cream, mask and the like, can also comprise any other substances which have physiological activity and are suitable for preparing the cosmetics, and can also comprise auxiliary materials acceptable for preparing the cosmetics. The hydrophobic cavity of the cyclodextrin molecule is selected and utilized, so that the tetrahydropiperine enters the hydrophobic cavity to realize the embedding of the molecule, the direct irritation of the tetrahydropiperine to the skin is greatly reduced, and the tetrahydropiperine can be completely dissolved in water. Moreover, under the action of molecular synergy, the permeation promoting effect of the novel penetrant based on the tetrahydropiperine cyclodextrin inclusion compound is better than that of the penetrant based on the simple cyclodextrin-embedded tetrahydropiperine.
Drawings
FIG. 1 is a schematic structural diagram of a penetrant performance testing device based on tetrahydropiperine cyclodextrin inclusion compound according to the present invention;
FIG. 2 is a graph of the effect of tranexamic acid in the presence of a tetrahydropiperine cyclodextrin inclusion compound-based osmotic agent of the present invention;
FIG. 3 is a flow diagram of a process for preparing an osmotic agent based on tetrahydropiperine cyclodextrin inclusion compound according to the present invention;
reference numbers in the figures: 1. a tank body; 2. an upper cover; 3. a cover glass; 4. a medicament; 5. skin or skin substitute; 6. an elastic clip; 7. a sampling tube; 8. a sampling needle.
Detailed Description
The invention is described in further detail below with reference to the following figures and detailed description:
the first embodiment is as follows:
the invention provides a penetrant based on a tetrahydropiperine cyclodextrin inclusion compound, which comprises the following components in percentage by mass: butanediol, glycerol, betaine, tetrahydropiperine cyclodextrin inclusion compound, hydrolyzed chitin, inositol and polylysine, wherein the tetrahydropiperine cyclodextrin inclusion compound comprises tetrahydropiperine and hydroxypropyl cyclodextrin, and the weight ratio of the tetrahydropiperine to the hydroxypropyl cyclodextrin is 1: 10.
Specifically, the tetrahydropiperine cyclodextrin inclusion compound solution is 21.9 parts, wherein the hydroxypropyl cyclodextrin accounts for 10 parts, and the tetrahydropiperine accounts for 1 part. 50 parts of butanediol, 10 parts of glycerol, 10 parts of betaine, 4 parts of hydrolyzed chitin, 4 parts of inositol and 0.1 part of polylysine.
The invention also provides a preparation method of the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound, which comprises the following steps:
(1) preparing a cyclodextrin solution, adding 10 parts of hydroxypropyl cyclodextrin into water, heating and stirring to fully dissolve the hydroxypropyl cyclodextrin to obtain a propyl cyclodextrin solution;
(2) adding 1 part of tetrahydropiperine into hydroxypropyl cyclodextrin water solution, heating and stirring at 40-60 ℃, and simultaneously using ultrasonic dispersion to completely dissolve the tetrahydropiperine into the hydroxypropyl cyclodextrin solution;
(3) keeping the temperature unchanged, and continuously stirring for 2-10 hours to fully embed the tetrahydropiperine by hydroxypropyl cyclodextrin;
(4) evaporating water to obtain tetrahydropiperine cyclodextrin clathrate;
(5) preparing 21.9 parts of tetrahydropiperine cyclodextrin inclusion compound solution, adding 50 parts of butanediol, 10 parts of glycerol, 10 parts of betaine, 4 parts of hydrolyzed chitin, 4 parts of inositol and 0.1 part of polylysine into the tetrahydropiperine cyclodextrin inclusion compound solution, and heating and stirring at 40-60 ℃ to form uniform solution; the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound is prepared.
Example two:
the invention provides a penetrant based on a tetrahydropiperine cyclodextrin inclusion compound, which comprises the following components in percentage by mass: butanediol, glycerol, betaine, tetrahydropiperine cyclodextrin inclusion compound, hydrolyzed chitin, inositol and polylysine, wherein the tetrahydropiperine cyclodextrin inclusion compound comprises tetrahydropiperine and hydroxypropyl cyclodextrin, and the weight ratio of the tetrahydropiperine to the hydroxypropyl cyclodextrin is 1: 10.
Specifically, the tetrahydropiperine cyclodextrin inclusion compound solution is 45.95 parts, wherein the hydroxypropyl cyclodextrin is 10 parts, and the tetrahydropiperine is 1 part. 40 parts butanediol, 5 parts glycerol, 5 parts betaine, 2 parts hydrolyzed chitin, 2 parts inositol, 0.05 parts polylysine.
The invention also provides a preparation method of the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound, which comprises the following steps:
(1) preparing a cyclodextrin solution, adding 10 parts of hydroxypropyl cyclodextrin into water, heating and stirring to fully dissolve the hydroxypropyl cyclodextrin to obtain a propyl cyclodextrin solution;
(2) adding 1 part of tetrahydropiperine into hydroxypropyl cyclodextrin water solution, heating and stirring at 40-60 ℃, and simultaneously using ultrasonic dispersion to completely dissolve the tetrahydropiperine into the hydroxypropyl cyclodextrin solution;
(3) keeping the temperature unchanged, and continuously stirring for 2-10 hours to fully embed the tetrahydropiperine by hydroxypropyl cyclodextrin;
(4) evaporating water to obtain tetrahydropiperine cyclodextrin clathrate;
(5) preparing 45.95 parts of tetrahydropiperine cyclodextrin inclusion compound solution, adding 40 parts of butanediol, 5 parts of glycerol, 5 parts of betaine, 2 parts of chitin hydrolysate, 2 parts of inositol and 0.05 part of polylysine into the tetrahydropiperine cyclodextrin inclusion compound solution, and heating and stirring at 40-60 ℃ to form uniform solution; the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound is prepared.
Example three:
the invention provides a penetrant based on a tetrahydropiperine cyclodextrin inclusion compound, which comprises the following components in percentage by mass: butanediol, glycerol, betaine, tetrahydropiperine cyclodextrin inclusion compound, hydrolyzed chitin, inositol and polylysine, wherein the tetrahydropiperine cyclodextrin inclusion compound comprises tetrahydropiperine and hydroxypropyl cyclodextrin, and the weight ratio of the tetrahydropiperine to the hydroxypropyl cyclodextrin is 1: 10.
Specifically, 35.92 parts of tetrahydropiperine cyclodextrin inclusion compound solution, wherein 10 parts of hydroxypropyl cyclodextrin is contained, and 1 part of tetrahydropiperine is contained. Butanediol has 45 parts, glycerol has 6 parts, betaine has 7 parts, hydrolyzed chitin has 3 parts, inositol has 3 parts, polylysine has 0.08 part.
The invention also provides a preparation method of the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound, which comprises the following steps:
(1) preparing a cyclodextrin solution, adding 10 parts of hydroxypropyl cyclodextrin into water, heating and stirring to fully dissolve the hydroxypropyl cyclodextrin to obtain a propyl cyclodextrin solution;
(2) adding 1 part of tetrahydropiperine into hydroxypropyl cyclodextrin water solution, heating and stirring at 40-60 ℃, and simultaneously using ultrasonic dispersion to completely dissolve the tetrahydropiperine into the hydroxypropyl cyclodextrin solution;
(3) keeping the temperature unchanged, and continuously stirring for 2-10 hours to fully embed the tetrahydropiperine by hydroxypropyl cyclodextrin;
(4) evaporating water to obtain tetrahydropiperine cyclodextrin clathrate;
(5) preparing 35.92 parts of tetrahydropiperine cyclodextrin inclusion compound solution, adding 45 parts of butanediol, 6 parts of glycerol, 7 parts of betaine, 3 parts of hydrolyzed chitin, 3 parts of inositol and 0.08 part of polylysine into the tetrahydropiperine cyclodextrin inclusion compound solution, and heating and stirring at 40-60 ℃ to form uniform solution; the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound is prepared.
Example four:
the invention provides a penetrant based on a tetrahydropiperine cyclodextrin inclusion compound, which comprises the following components in percentage by mass: butanediol, glycerol, betaine, tetrahydropiperine cyclodextrin inclusion compound, hydrolyzed chitin, inositol and polylysine, wherein the tetrahydropiperine cyclodextrin inclusion compound comprises tetrahydropiperine and hydroxypropyl cyclodextrin, and the weight ratio of the tetrahydropiperine to the hydroxypropyl cyclodextrin is 1: 1.
Specifically, 35.95 parts of tetrahydropiperine cyclodextrin inclusion compound solution, wherein 5 parts of hydroxypropyl cyclodextrin and 5 parts of tetrahydropiperine are used. Butanediol has a value of 46 parts, glycerol has a value of 6 parts, betaine has a value of 6 parts, hydrolysed chitin has a value of 3 parts, inositol has a value of 3 parts and polylysine has a value of 0.05 part.
The invention also provides a preparation method of the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound, which comprises the following steps:
(1) preparing a cyclodextrin solution, adding 5 parts of hydroxypropyl cyclodextrin into water, heating and stirring to fully dissolve the hydroxypropyl cyclodextrin to obtain a propyl cyclodextrin solution;
(2) adding 5 parts of tetrahydropiperine into hydroxypropyl cyclodextrin water solution, heating and stirring at 40-60 ℃, and simultaneously using ultrasonic dispersion to completely dissolve the tetrahydropiperine into the hydroxypropyl cyclodextrin solution;
(3) keeping the temperature unchanged, and continuously stirring for 2-10 hours to fully embed the tetrahydropiperine by hydroxypropyl cyclodextrin;
(4) evaporating water to obtain tetrahydropiperine cyclodextrin clathrate;
(5) preparing 35.95 parts of tetrahydropiperine cyclodextrin inclusion compound solution, adding 46 parts of butanediol, 6 parts of glycerol, 6 parts of betaine, 3 parts of hydrolyzed chitin, 3 parts of inositol and 0.05 part of polylysine into the tetrahydropiperine cyclodextrin inclusion compound solution, and heating and stirring at 40-60 ℃ to form uniform solution; the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound is prepared.
Example five:
the effect test of the penetrant based on the tetrahydropiperine cyclodextrin inclusion compound is carried out, as shown in fig. 1, a vertical diffusion pool is required to be used during the test, the vertical diffusion pool comprises a pool body, an upper cover covering the pool body is arranged on the pool body, two ends of the upper cover are opened, the interior of the upper cover is communicated with the interior of the pool body, a cover glass is covered on the upper end of the upper cover, a sampling pipe which extends obliquely upwards and is communicated with the interior of the pool body is arranged on one side of the pool body, and a sampling needle is inserted in the sampling pipe.
During the test, a magnetic stirrer is put into the cell body, the skin or the skin substitute is covered on the cell body, the upper cover is arranged on the cell body, and the skin or the skin substitute is tightly pressed by the upper cover. The tank body and the upper cover are clamped by using an elastic clamp, 0.5 percent of the penetrant in the first embodiment of the invention is added into 2 percent of tranexamic acid, and a mixed solution of 2 percent of tranexamic acid and 0.5 percent of the penetrant based on the tetrahydro piperine cyclodextrin inclusion compound of the invention is added into the tank body. And covering the cover glass on the upper cover, placing the tank body on a magnetic stirrer, and driving the magnetic stirrer to rotate to easily stir in the tank body. After a period of time, the mixed solution in the pool body is taken out through a sampling tube, and the content of the tranexamic acid in the solution is detected.
In order to improve the accuracy of the experiment, three experiments were performed, and the average of the results of the three experiments was taken, and the results are shown in table 1, table 2, and fig. 2. The experimental result shows that the penetration rate of the tranexamic acid is 7.6 times that of the tranexamic acid without the plant penetrating agent after 0.5 percent of the penetrating agent is added, and the transdermal absorption of the tranexamic acid is obviously promoted.
Example six:
to determine the effect of inositol on the osmotic agents of the present invention, comparative tests were performed with and without inositol.
0.5% of the penetrant of example one of the present invention is added to 2% of tranexamic acid, and a mixed solution of 2% of tranexamic acid and 0.5% of the penetrant based on tetrahydropiperine cyclodextrin inclusion compound of the present invention is added to the tank body. And covering the cover glass on the upper cover, placing the tank body on a magnetic stirrer, and driving the magnetic stirrer to rotate to easily stir in the tank body. After a period of time, the mixed solution in the pool body is taken out through a sampling tube, and the content of the tranexamic acid in the solution is detected.
Preparing an inositol-free penetrant 1, wherein the penetrant 1 comprises the following components: butanediol, glycerol, betaine, tetrahydropiperine cyclodextrin inclusion compound and polylysine, wherein the tetrahydropiperine cyclodextrin inclusion compound comprises tetrahydropiperine and cyclodextrin, and the weight ratio of the tetrahydropiperine to the cyclodextrin is 1: 10. The tetrahydropiperine cyclodextrin inclusion compound solution comprises 21.9 parts by mass, wherein 10 parts of hydroxypropyl cyclodextrin is contained, and 1 part of tetrahydropiperine is contained. 50 parts of butanediol, 10 parts of glycerol, 10 parts of betaine, 4 parts of hydrolyzed chitin and 0.1 part of polylysine. The preparation of the penetrant 1 comprises the following steps: (1) preparing a cyclodextrin solution, adding 10 parts of hydroxypropyl cyclodextrin into water, heating and stirring to fully dissolve the hydroxypropyl cyclodextrin to obtain a propyl cyclodextrin solution; (2) adding 1 part of tetrahydropiperine into hydroxypropyl cyclodextrin water solution, heating and stirring at 40-60 ℃, and simultaneously using ultrasonic dispersion to completely dissolve the tetrahydropiperine into the hydroxypropyl cyclodextrin solution; (3) keeping the temperature unchanged, and continuously stirring for 2-10 hours to fully embed the tetrahydropiperine by hydroxypropyl cyclodextrin; (4) evaporating water to obtain tetrahydropiperine cyclodextrin clathrate; (5) preparing 21.9 parts of tetrahydropiperine cyclodextrin inclusion compound solution, adding 50 parts of butanediol, 10 parts of glycerol, 10 parts of betaine, 4 parts of hydrolyzed chitin and 0.1 part of polylysine into the tetrahydropiperine cyclodextrin inclusion compound solution, and heating and stirring at 40-60 ℃ to form uniform solution; the penetrant 1 is prepared.
0.5% of penetrant 1 is added into 2% of tranexamic acid, and a mixed solution of 2% of tranexamic acid and 0.5% of penetrant 1 is added into the tank body. And covering the cover glass on the upper cover, placing the tank body on a magnetic stirrer, and driving the magnetic stirrer to rotate to easily stir in the tank body. After a period of time, the mixed solution in the pool body is taken out through a sampling tube, and the content of the tranexamic acid in the solution is detected. As can be seen from table 3, chitin and inositol in the osmotic agent based on the tetrahydropiperine cyclodextrin inclusion compound of the present invention have an enhanced effect on the permeation promotion of tetrahydropiperine.
Table 3 comparative test table of subcutaneous permeability of penetrant 1 and penetrant of the present invention
Example seven:
to determine the effect of tetrahydropiperine cyclodextrin inclusion compounds on the efficacy of the penetrants of the present invention, comparative tests of the efficacy of penetrants containing tetrahydropiperine cyclodextrin inclusion compounds and penetrants not containing tetrahydropiperine cyclodextrin inclusion compounds were conducted.
0.5% of the penetrant of example one of the present invention is added to 2% of tranexamic acid, and a mixed solution of 2% of tranexamic acid and 0.5% of the penetrant based on tetrahydropiperine cyclodextrin inclusion compound of the present invention is added to the tank body. And covering the cover glass on the upper cover, placing the tank body on a magnetic stirrer, and driving the magnetic stirrer to rotate to easily stir in the tank body. After a period of time, the mixed solution in the pool body is taken out through a sampling tube, and the content of the tranexamic acid in the solution is detected.
Preparing a penetrant 2, wherein the penetrant 2 comprises the following components: 50 parts of butanediol, 10 parts of glycerol, 10 parts of betaine, 4 parts of hydrolyzed chitin and 0.1 part of polylysine in percentage by mass. The preparation of the penetrant 2 comprises the following steps: adding 10 parts of glycerol, 10 parts of betaine, 4 parts of hydrolyzed chitin and 0.1 part of polylysine into 50 parts of butanediol, and heating and stirring at 40-60 ℃ to form a uniform solution to obtain the penetrant 2.
0.5% of penetrant 2 is added into 2% of tranexamic acid, and a mixed solution of 2% of tranexamic acid and 0.5% of penetrant 2 is added into the tank body. And covering the cover glass on the upper cover, placing the tank body on a magnetic stirrer, and driving the magnetic stirrer to rotate to easily stir in the tank body. After a period of time, the mixed solution in the pool body is taken out through a sampling tube, and the content of the tranexamic acid in the solution is detected. From table 4, it can be seen that under the action of molecular synergy, the permeation enhancer based on the tetrahydropiperine cyclodextrin inclusion compound of the present invention has better permeation enhancing effect than that of the simple cyclodextrin-embedded tetrahydropiperine.
Table 4 comparative test table of subcutaneous permeability of penetrant of the present invention and penetrant 2
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (6)
1. A penetrant based on tetrahydropiperine cyclodextrin inclusion compound is characterized by comprising the following components: the high-efficiency synthesis method comprises the following steps of butanediol, glycerol, betaine, tetrahydropiperine cyclodextrin inclusion compound, hydrolyzed chitin, inositol and polylysine, wherein the tetrahydropiperine cyclodextrin inclusion compound comprises the tetrahydropiperine and cyclodextrin, and the weight ratio of the tetrahydropiperine to the cyclodextrin is 1 (1.0-10).
2. The tetrahydropiperine cyclodextrin inclusion compound of claim 1, wherein the butylene glycol is 40-50%, the glycerol is 5-10%, the tetrahydropiperine cyclodextrin inclusion compound is 21.9-45.95%, the betaine is 5-10%, the hydrolyzed chitin is 2-4%, the inositol is 2-4%, and the polylysine is 0.05-0.1% by weight.
3. The tetrahydropiperine cyclodextrin inclusion compound of claim 2, wherein the cyclodextrin is hydroxypropyl- β -cyclodextrin.
4. A preparation method of a penetrant based on a tetrahydropiperine cyclodextrin inclusion compound is characterized by comprising the following steps:
(1) preparing a cyclodextrin solution, adding cyclodextrin into water, heating and stirring to fully dissolve the cyclodextrin to prepare a propylcyclodextrin solution;
(2) adding tetrahydropiperine into cyclodextrin water solution, heating and stirring at 40-60 ℃, and simultaneously using ultrasonic dispersion to completely dissolve the tetrahydropiperine into the cyclodextrin solution;
(3) keeping the temperature unchanged, and continuously stirring for 2-10 hours to fully embed the tetrahydropiperine by the cyclodextrin;
(4) evaporating water to obtain tetrahydropiperine cyclodextrin clathrate;
(5) preparing a tetrahydropiperine cyclodextrin inclusion compound solution, adding butanediol, glycerol, betaine, hydrolyzed chitin, inositol and polylysine into the tetrahydropiperine cyclodextrin inclusion compound solution, and heating and stirring at 40-60 ℃ to form a uniform solution.
5. The method of claim 4, wherein the cyclodextrin is hydroxypropyl- β -cyclodextrin.
6. The method for preparing the osmotic agent based on the tetrahydropiperine cyclodextrin inclusion compound according to claim 4, wherein the butanediol is 40-50%, the glycerol is 5-10%, the tetrahydropiperine cyclodextrin inclusion compound is 21.9% -45.95%, the betaine is 5-10%, the hydrolyzed chitin is 2-4%, the inositol is 2-4%, and the polylysine is 0.05-0.1% by mass.
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| CN117919121A (en) * | 2024-03-04 | 2024-04-26 | 广州科盈化妆品有限公司 | Tetrahydropiperine-cyclodextrin inclusion composition and preparation method and application thereof |
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