CN113576944A - Freeze-dried ball and preparation method thereof and skin care product - Google Patents
Freeze-dried ball and preparation method thereof and skin care product Download PDFInfo
- Publication number
- CN113576944A CN113576944A CN202110906352.3A CN202110906352A CN113576944A CN 113576944 A CN113576944 A CN 113576944A CN 202110906352 A CN202110906352 A CN 202110906352A CN 113576944 A CN113576944 A CN 113576944A
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- China
- Prior art keywords
- freeze
- skin care
- solution
- percent
- excipient
- Prior art date
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- Granted
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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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0216—Solid or semisolid forms
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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
- A61K8/60—Sugars; 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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products 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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
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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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening 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
- A61K2800/52—Stabilizers
- A61K2800/524—Preservatives
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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
- A61K2800/59—Mixtures
- A61K2800/592—Mixtures of compounds complementing their respective functions
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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
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/84—Products or compounds obtained by lyophilisation, freeze-drying
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to the technical field of skin care products, and particularly relates to a freeze-dried ball, a preparation method thereof and a skin care product. The freeze-dried ball comprises the following components in percentage by mass: 2 to 10 percent of small molecular excipient, 0.1 to 1 percent of high molecular excipient, 0.01 to 5 percent of physiologically acceptable skin care active ingredients, pH regulator and water; the pH regulator is at least one of ascorbic acid, ascorbyl glucoside, lactobionic acid and mandelic acid, and maintains pH of the lyophilized stock solution below 3. The freeze-dried ball can avoid microbial contamination. The invention also provides a preparation method of the freeze-dried ball and a skin care product comprising the freeze-dried ball.
Description
Technical Field
The invention relates to the technical field of skin care products, and particularly relates to a freeze-dried ball, a preparation method thereof and a skin care product.
Background
In the field of skin care products, consumers have a high expectation on the appearance of freeze-dried products. The ordinary penicillin bottle package can not meet the pursuit of the beauty of consumers. Therefore, the blister is widely used as a freeze-dried product packaging material for replacing a penicillin bottle, however, the freeze-dried product manufactured by using the blister is usually realized by in-situ freeze-drying, namely freeze-drying by using a mold and transferring the mold for filling the blister. However, since no preservative is added to the formulation of the lyophilized product, the original solution before lyophilization must be sterilized (usually by filtration) in order to prevent contamination of the product by microorganisms. At the same time, the freeze-drying production plant needs to maintain a sterile environment. Even so, lyophilized products, especially non-in situ lyophilized products, still have a high risk of microbial contamination because of the need for filling or transfer.
Disclosure of Invention
Based on the freeze-dried balls, the invention provides freeze-dried balls without microbial pollution, a preparation method thereof and a skin care product.
The invention provides a freeze-dried ball which comprises the following components in percentage by mass:
2 to 10 percent of small molecular excipient, 0.1 to 1 percent of high molecular excipient, 0.01 to 5 percent of physiologically acceptable skin care active ingredients, pH regulator and water;
the pH regulator is at least one of ascorbic acid, ascorbyl glucoside, lactobionic acid and mandelic acid, and maintains the pH value of the lyophilized stock solution less than 3.
Optionally, the freeze-dried spheres as described above, wherein the small molecule excipient is at least one of mannitol, sorbitol, sucrose and trehalose;
the macromolecular excipient is at least one of pullulan polysaccharide, glucan, chitosan, sodium hyaluronate, polyvinylpyrrolidone, polyethylene glycol and hydroxypropyl methyl cellulose.
Optionally, the freeze-dried spheres as described above, the physiologically acceptable skin care active ingredient is at least one of niacinamide, carnosine, tranexamic acid, glutathione, tea polyphenols, and tannic acid.
The invention also provides a preparation method of the freeze-dried ball, which comprises the following steps:
dissolving the small molecular excipient, the high molecular excipient, the physiologically acceptable skin care active component and the pH regulator in water, injecting the obtained solution into a mold, freezing and shaping, demolding, and freeze-drying.
Optionally, in the preparation method of the freeze-dried ball, the solution is subjected to filtration sterilization, and the pore size of a filter element used for the filtration sterilization is 0.2 μm to 0.5 μm.
Optionally, in the preparation method of the freeze-dried ball, the temperature for the solution to be injected into the mould for freeze setting is-20 ℃ to-30 ℃.
Optionally, in the preparation method of the freeze-dried ball, the freeze-drying temperature is-25 ℃ to 30 ℃ and the time is 15h to 25 h.
Optionally, the preparation method of the freeze-dried ball further comprises the step of packaging the freeze-dried product in a non-oxidizing atmosphere with the temperature of 35-45 ℃ and the humidity of less than 10%.
In still another aspect of the present invention, there is further provided a skin care product comprising the lyophilized pellet described above.
Optionally, as described above, the skin care product is a liquid skin care product or a solid skin care product, the liquid skin care product includes at least one of an emulsion, a water agent, an oil agent and a spray, and the solid skin care product includes at least one of an ointment, a cream, a film agent and a gel.
According to research and invention, the small molecular excipient and the high molecular excipient are cooperatively used, so that the high molecular excipient has better re-solubility on the basis of ensuring the forming. The growth of microorganisms can be inhibited by further combining a pH regulator on the basis of not influencing the basic efficacy of the freeze-dried balls, so that the risk of pollution of the freeze-dried balls in the process of preparing the freeze-dried balls in an ex-situ manner is effectively reduced.
Detailed Description
Reference will now be made in detail to embodiments of the invention, one or more examples of which are described below. Each example is provided by way of explanation, not limitation, of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. For instance, features illustrated or described as part of one embodiment, can be used on another embodiment to yield a still further embodiment.
It is therefore intended that the present invention cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents. Other objects, features and aspects of the present invention are disclosed in or are apparent from the following detailed description. It is to be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only, and is not intended as limiting the broader aspects of the present invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
Other than as shown in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients, physical and chemical properties, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about". For example, unless indicated to the contrary, the numerical parameters set forth in the foregoing specification and attached claims are approximations that can be suitably varied by those skilled in the art in seeking to obtain the desired properties utilizing the teachings disclosed herein. The use of numerical ranges by endpoints includes all numbers within that range and any range within that range, for example, 1 to 5 includes 1, 1.1, 1.3, 1.5, 2, 2.75, 3, 3.80, 4, and 5, and the like.
The invention provides a freeze-dried ball which comprises the following components in percentage by mass:
2 to 10 percent of small molecular excipient, 0.1 to 1 percent of high molecular excipient, 0.01 to 5 percent of physiologically acceptable skin care active ingredients, pH regulator and water;
the pH regulator is at least one of ascorbic acid, ascorbyl glucoside, lactobionic acid and mandelic acid, and maintains pH of the lyophilized stock solution below 3.
The small molecular excipient and the high molecular excipient are used cooperatively, so that the high molecular excipient has better re-solubility on the basis of ensuring the forming. The growth of microorganisms can be inhibited by further combining a pH regulator on the basis of not influencing the basic efficacy of the freeze-dried balls, so that the risk of pollution of the freeze-dried balls in the process of preparing the freeze-dried balls in an ex-situ manner is effectively reduced. Moreover, the pH regulator selected by the invention also has the whitening effect and does not influence the forming of the freeze-dried ball.
In some embodiments, the mass percentage of the small molecule excipient may also be 3%, 4%, 5%, 6%, 7%, 8%, 9%; the content of the polymer excipient may be 0.2%, 0.3%, 0.5%, 0.6%, 0.8%, 0.9% by mass.
In some embodiments, the small molecule excipient has a molecular weight of 150Da to 600Da and the high molecule excipient has a molecular weight of 100kDa to 5000 kDa.
In some embodiments, the small molecule excipient is at least one of mannitol, sorbitol, sucrose, and trehalose. Preferably, the small molecule excipient is mannitol and trehalose.
In some embodiments, the macromolecular excipient is at least one of pullulan, dextran, chitosan, sodium hyaluronate, polyvinylpyrrolidone, polyethylene glycol, and hydroxypropyl methylcellulose. Preferably, the macromolecular excipients are pullulan and dextran.
In some embodiments, the total weight percentage of the pH adjuster is 2% to 4%.
In some embodiments, the pH of the lyophilized stock solution is maintained between 2 and 3.
In some embodiments, the physiologically acceptable skin care active ingredient is not limited, and any one commonly used in the art may be selected, for example, the physiologically acceptable skin care active ingredient having whitening and spot-removing effects, the physiologically acceptable skin care active ingredient having moisturizing and moisturizing effects, the physiologically acceptable skin care active ingredient having oil-controlling effects, the physiologically acceptable skin care active ingredient having wrinkle-removing and anti-aging effects, the physiologically acceptable skin care active ingredient having sunscreen effects, or two or more ingredients selected from these effects. It is noted that, since the pH of the lyophilized pellet is required to be less than 3 in the present invention, the selected physiologically acceptable skin care active ingredient is stable at the pH, and may be one or more of niacinamide, carnosine, tranexamic acid, glutathione, tea polyphenols and tannic acid, for example.
The tripeptide containing gamma-amido bond and sulfhydryl group in the glutathione is formed by combining glutamic acid, cysteine and glycine, has the effects of whitening, inhibiting the generation of melanin to a certain extent, delaying senility and integrating detoxification. The nicotinamide is also called nicotinamide, is an amide compound of nicotinic acid, has the main effects on skin aging resistance that dark, yellow and vegetable colors of skin color generated in the early aging process can be relieved and prevented, damaged skin stratum corneum lipid barrier can be repaired, and skin resistance is improved; in addition, the product also has deep water-retaining and moisturizing effects. The tranexamic acid is tranexamic acid and tranexamic acid, can block the transfer of melanin and accelerate metabolism, and has the effects of removing black and removing speckles which are about 50 times higher than that of vitamin C and about 10 times higher than that of fruit acid. The tannic acid is also called tannic acid, and has effects of controlling oil, preventing sunburn, brightening skin and tightening skin. The tea polyphenol is also called antioxidant, vitamin and Fanghailing, is a compound of polyhydroxy phenolic compounds in tea, consists of more than 30 phenolic substances, and mainly comprises the following components: flavanones, anthocyanidins, flavonols, anthocyanins, phenolic acids and depside 6 compounds, wherein the flavanones are the most important, the content of the flavanones can reach 60-80%, and the flavanones are flavonoids, so that the flavanones have various physiological activities of oxidation resistance, radiation protection, aging resistance and the like.
The invention also provides a preparation method of the freeze-dried ball, which comprises the following steps:
dissolving small molecular excipient, high molecular excipient, physiologically acceptable skin care active component and pH regulator in water, filtering the obtained solution with filter element, filling into mold, freeze-drying, demolding, and freeze-drying.
The method comprises the following specific steps:
s1: putting the macromolecular excipient into water, heating to 70-90 ℃, and preserving heat until the macromolecular excipient is dissolved;
s2: cooling to 25-35 ℃, adding a small molecular excipient and physiologically acceptable skin care active ingredients, dissolving, and adding a pH regulator;
s3: filtering the solution for sterilization, injecting into a mold for freeze-setting, demolding, and freeze-drying.
In some embodiments, the filter element used in the filter sterilization has a pore size of 0.2 μm to 0.5. mu.m. Preferably, the pore size of the filter element is 0.22 μm.
In some embodiments, the material of the mold is not limited, and the material commonly used in the art is selected, and a silicone mold is preferred for the convenience of demolding and uniform heat transfer.
In some embodiments, the freezing temperature of the mold after the liquid injection is from-20 ℃ to-30 ℃ for 0.5h to 1.5 h.
In some embodiments, the temperature of lyophilization is from-25 ℃ to 30 ℃ for 15h to 25 h.
In some embodiments, the preparation method further comprises the step of packaging the freeze-dried product in a non-oxidizing atmosphere with a humidity of less than 10% at a temperature of 35 ℃ to 45 ℃.
In some embodiments, the non-oxidizing atmosphere may be a nitrogen atmosphere, an argon atmosphere, or a helium atmosphere.
In still another aspect of the present invention, there is further provided a skin care product comprising the lyophilized pellet described above.
In some embodiments, the skin care product is a liquid skin care product comprising at least one of an emulsion, a lotion, an oil, and a spray, or a solid skin care product comprising at least one of an ointment, a cream, a film, and a gel.
In some embodiments, the skin care product comprises a serum, a lotion, an emulsion, a cream, a moisturizer, a mask.
Example 1
Weighing 0.5 percent of pullulan and 0.5 percent of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the solution to 80 ℃ until the pullulan and the glucan are completely dissolved. Then the temperature is reduced to 30 ℃, mannitol with the mass percentage of 5%, trehalose with the mass percentage of 5%, ascorbic acid with the mass percentage of 2%, ascorbyl glucoside with the mass percentage of 2% and glutathione with the mass percentage of 0.1% are added, and the mixture is stirred until the mixture is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Example 2
Weighing 0.5 percent of pullulan polysaccharide by mass percent respectively, putting the pullulan polysaccharide into water, and heating the water to 80 ℃ until the pullulan polysaccharide is completely dissolved. Then the temperature is reduced to 30 ℃, mannitol with the mass percentage of 5%, ascorbic acid with the mass percentage of 2% and glutathione with the mass percentage of 0.1% are added, and the mixture is stirred until the mixture is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Example 3
0.5 percent of glucan in percentage by mass is weighed and put into water and heated to 80 ℃ until the glucan is completely dissolved. Then, the temperature is reduced to 30 ℃, trehalose with the mass percentage of 5%, ascorbic acid glucoside with the mass percentage of 2% and glutathione with the mass percentage of 0.1% are added, and the mixture is stirred until the trehalose is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Example 4
Weighing 0.1% of pullulan and 0.4% of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the solution to 80 ℃ until the pullulan and the glucan are completely dissolved. Then the temperature is reduced to 30 ℃, mannitol with the mass percentage of 4%, trehalose with the mass percentage of 1%, ascorbyl glucoside with the mass percentage of 2% and glutathione with the mass percentage of 0.1% are added, and the mixture is stirred until the mixture is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Example 5
Weighing 0.25 percent of pullulan and 0.25 percent of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the solution to 80 ℃ until the pullulan and the glucan are completely dissolved. Then the temperature is reduced to 30 ℃, mannitol with the mass percentage of 2.5%, trehalose with the mass percentage of 2.5%, ascorbic acid with the mass percentage of 1%, ascorbyl glucoside with the mass percentage of 1% and glutathione with the mass percentage of 0.1% are added, and the mixture is stirred until the mixture is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Example 6
Weighing 0.4 percent of pullulan and 0.1 percent of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the solution to 80 ℃ until the pullulan and the glucan are completely dissolved. Then the temperature is reduced to 30 ℃, mannitol with the mass percentage of 4%, trehalose with the mass percentage of 1%, ascorbic acid with the mass percentage of 2%, ascorbyl glucoside with the mass percentage of 1% and glutathione with the mass percentage of 0.1% are added, and the mixture is stirred until the mixture is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Comparative example 1
This comparative example was prepared substantially the same as example 1, except that: no pH adjuster was added. The method comprises the following specific steps:
weighing 0.5 percent of pullulan and 0.5 percent of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the solution to 80 ℃ until the pullulan and the glucan are completely dissolved. Then, the temperature is reduced to 30 ℃, mannitol with the mass percentage of 5%, trehalose with the mass percentage of 5% and glutathione with the mass percentage of 0.1% are added, and the mixture is stirred until the mixture is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Comparative example 2
This comparative example was prepared substantially the same as example 2, except that: no pH adjuster was added. The method comprises the following specific steps:
weighing 0.5 percent of pullulan polysaccharide by mass percent respectively, putting the pullulan polysaccharide into water, and heating the water to 80 ℃ until the pullulan polysaccharide is completely dissolved. Then, the temperature is reduced to 30 ℃, mannitol with the mass percentage of 5% and glutathione with the mass percentage of 0.1% are added, and the mixture is stirred until the mixture is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Comparative example 3
This comparative example was prepared substantially the same as example 3, except that: no pH adjuster was added. The method comprises the following specific steps:
0.5 percent of glucan in percentage by mass is weighed and put into water and heated to 80 ℃ until the glucan is completely dissolved. Then, the temperature is reduced to 30 ℃, trehalose with the mass percentage of 5 percent and glutathione with the mass percentage of 0.1 percent are added, and the mixture is stirred until the trehalose is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Comparative example 4
This comparative example was prepared essentially the same as example 4, except that: no pH adjuster was added. The method comprises the following specific steps:
weighing 0.1% of pullulan and 0.4% of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the solution to 80 ℃ until the pullulan and the glucan are completely dissolved. Then cooling to 30 ℃, adding mannitol with the mass percentage of 4%, trehalose with the mass percentage of 1% and glutathione with the mass percentage of 0.1%, and stirring until the mannitol, the trehalose and the glutathione are completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Comparative example 5
This comparative example was prepared substantially the same as example 5, except that: no pH adjuster was added. The method comprises the following specific steps:
weighing 0.25 percent of pullulan and 0.25 percent of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the solution to 80 ℃ until the pullulan and the glucan are completely dissolved. Then the temperature is reduced to 30 ℃, mannitol with the mass percentage of 2.5 percent, trehalose with the mass percentage of 2.5 percent and glutathione with the mass percentage of 0.1 percent are added, and the mixture is stirred until the mixture is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Comparative example 6
This comparative example was prepared essentially the same as example 6, except that: no pH adjuster was added. The method comprises the following specific steps:
weighing 0.4 percent of pullulan and 0.1 percent of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the solution to 80 ℃ until the pullulan and the glucan are completely dissolved. Then cooling to 30 ℃, adding mannitol with the mass percentage of 4%, trehalose with the mass percentage of 1% and glutathione with the mass percentage of 0.1%, and stirring until the mannitol, the trehalose and the glutathione are completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Comparative example 7
This comparative example was prepared substantially the same as example 1, except that: the total mass percentage of pullulan and dextran is different. The method comprises the following specific steps:
weighing 1% of pullulan and 1% of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the mixture to 80 ℃ until the pullulan and the glucan are completely dissolved. Then the temperature is reduced to 30 ℃, mannitol with the mass percentage of 5%, trehalose with the mass percentage of 5%, ascorbic acid with the mass percentage of 2%, ascorbyl glucoside with the mass percentage of 2% and glutathione with the mass percentage of 0.1% are added, and the mixture is stirred until the mixture is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Comparative example 8
This comparative example was prepared substantially the same as example 1, except that: the total mass percentage of mannitol and trehalose are different. The method comprises the following specific steps:
weighing 0.5 percent of pullulan and 0.5 percent of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the solution to 80 ℃ until the pullulan and the glucan are completely dissolved. Then the temperature is reduced to 30 ℃, mannitol with the mass percentage of 0.5 percent, trehalose with the mass percentage of 0.5 percent, ascorbic acid with the mass percentage of 2 percent, ascorbyl glucoside with the mass percentage of 2 percent and glutathione with the mass percentage of 0.1 percent are added, and the mixture is stirred until the mixture is completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
Comparative example 9
This comparative example was prepared substantially the same as example 1, except that: the pH regulator is acetic acid and lactic acid. The method comprises the following specific steps:
weighing 0.5 percent of pullulan and 0.5 percent of glucan in percentage by mass respectively, putting the pullulan and the glucan in water, and heating the solution to 80 ℃ until the pullulan and the glucan are completely dissolved. Then cooling to 30 ℃, adding mannitol with the mass percentage of 5%, trehalose with the mass percentage of 5%, lactic acid with the mass percentage of 2%, acetic acid with the mass percentage of 2% and glutathione with the mass percentage of 0.1%, and stirring until the mannitol, the trehalose, the lactic acid, the acetic acid and the glutathione are completely dissolved. Then filtering and sterilizing the solution by a filter element with the diameter of 0.22 mu m, injecting the solution into a spherical silica gel mold (the silica gel mold injected with the solution is frozen in a flat plate prefreezing device with the temperature of-25 ℃ for 1 hour), and demolding to obtain the ice ball. The ice pellets were then placed in a freeze dryer and freeze dried for 20h with the temperature sequentially increasing from-25 ℃ to 30 ℃. And packaging the freeze-dried product in a nitrogen environment with the temperature of 40 ℃ and the humidity of less than 10%.
The freeze-dried balls prepared in each example and comparative example were subjected to the following performance tests:
the forming performance of the sphere is characterized by the shrinkage rate gamma of the diameter of the sphere, and the calculation method is as follows: γ is 1-a/b. Wherein, a is the diameter of the freeze-dried ball after freeze-drying, and b is the diameter of the ice ball before freeze-drying. From the definition of the shrinkage rate γ, the smaller the shrinkage rate, the better the freeze-drying molding performance of γ.
The re-solubility of the spheres was characterized by the collapse time of the spheres upon addition to water. The specific implementation method comprises the following steps: the individual lyophilized spheres were added to deionized water and the time from the contact of the spheres with the water surface to the complete collapse of the spheres was calculated.
And (3) detecting microorganisms: the lyophilized pellets prepared according to the preparation method in each of examples and comparative examples were each taken 10 pieces and dissolved in 10g of water, and left to stand in the atmosphere of the same environment for 24 hours for microbial detection.
The test results are shown in table 1:
table 1 freeze-dried pellet performance test results
| Results of microbial detection (cfu/mL) | Shrinkage rate gamma | Redissolution(s) | |
| Example 1 | 0 | 0.05 | 2.3 |
| Example 2 | 0 | 0.07 | 2.1 |
| Example 3 | 0 | 0.08 | 2.9 |
| Example 4 | 0 | 0.06 | 3.2 |
| Example 5 | 0 | 0.10 | 3.5 |
| Example 6 | 0 | 0.08 | 3.2 |
| Comparative example 1 | ＞500 | 0.02 | 2.7 |
| Comparative example 2 | 240 | 0.07 | 2.3 |
| Comparative example 3 | 136 | 0.06 | 2.7 |
| Comparative example 4 | ＞500 | 0.06 | 3.4 |
| Comparative example 5 | 150 | 0.09 | 2.0 |
| Comparative example 6 | 129 | 0.03 | 1.9 |
| Comparative example 7 | 0 | 0.02 | 93 |
| Comparative example 8 | 0 | 0.55 | >120 |
| Comparative example 9 | 0 | 0.74 | >120 |
As can be seen from Table 1, the lyophilized pellets of examples 1 to 6 had low risk of microorganisms without growth of microorganisms in an open environment, while the lyophilized pellets of comparative examples 1 to 6 were contaminated with microorganisms to different degrees in the same environment. The results demonstrate that the addition of a pH modifier significantly reduces the risk of contamination of the lyophilized pellet with microorganisms. Meanwhile, the shrinkage of the lyophilized pellets in examples 1 to 6 was small, indicating that the moldability was good. Shorter collapse times also indicate that the lyophilized pellet possesses better resolubility.
In contrast, comparative examples 7, 8 and 9 used different amounts of macromolecular excipient, small molecule excipient and different pH adjusting agent, respectively, compared to example 1. It can be seen from the experimental results that, although the lyophilized spheres of comparative examples 7, 8, 9 also have a lower risk of microorganisms, too much macromolecular excipient (comparative example 7) causes a significant decrease in the reconstitution speed; the use amount of the small molecular excipient is reduced (comparative example 8), and the re-solubility of the lyophilized pellet is obviously reduced while the forming performance of the lyophilized pellet is reduced; other pH adjustments are selected, which can also reduce the forming and redissolving properties of the lyophilized pellet.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. The freeze-dried ball is characterized by comprising the following components in percentage by mass:
2 to 10 percent of small molecular excipient, 0.1 to 1 percent of high molecular excipient, 0.01 to 5 percent of physiologically acceptable skin care active ingredients, pH regulator and water;
the pH regulator is at least one of ascorbic acid, ascorbyl glucoside, lactobionic acid and mandelic acid, and maintains the pH value of the lyophilized stock solution less than 3.
2. The lyophilized pellet according to claim 1, wherein the small molecule excipient is at least one of mannitol, sorbitol, sucrose and trehalose;
the macromolecular excipient is at least one of pullulan polysaccharide, glucan, chitosan, sodium hyaluronate, polyvinylpyrrolidone, polyethylene glycol and hydroxypropyl methyl cellulose.
3. The lyophilized pellet according to claim 1, wherein the physiologically acceptable skin care active ingredient is at least one of niacinamide, carnosine, tranexamic acid, glutathione, tea polyphenols, and tannic acid.
4. A method of preparing lyophilized pellets according to any one of claims 1 to 3, comprising the steps of:
dissolving the small molecular excipient, the high molecular excipient, the physiologically acceptable skin care active component and the pH regulator in water, injecting the obtained solution into a mold, freezing and shaping, demolding and freeze-drying.
5. The method for preparing lyophilized pellets according to claim 4, wherein the solution is sterilized by filtration, and the pore size of the filter element used for sterilization by filtration is 0.2 μm to 0.5 μm.
6. The method for preparing lyophilized pellet as claimed in claim 4, wherein the temperature of freezing and shaping after the solution is injected into the mold is-20 ℃ to-30 ℃.
7. The method for preparing lyophilized pellets according to claim 3, wherein the temperature of the lyophilization is-25 ℃ to 30 ℃ and the time is 15h to 25 h.
8. The preparation method of the lyophilized pellet as claimed in any one of claims 4 to 7, further comprising a step of packaging the lyophilized product in a non-oxidizing atmosphere at 35 ℃ to 45 ℃ and a humidity of less than 10%.
9. A skin care product comprising the lyophilized pellet as claimed in any one of claims 1 to 3.
10. The skin care product of claim 9, wherein the skin care product is a liquid skin care product or a solid skin care product, the liquid skin care product comprises at least one of an emulsion, a water agent, an oil agent and a spray, and the solid skin care product comprises at least one of an ointment, a cream, a film agent and a gel.
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