CN110974718A - Freeze-dried powder and preparation method thereof - Google Patents
Freeze-dried powder and preparation method thereof Download PDFInfo
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- CN110974718A CN110974718A CN201911416355.8A CN201911416355A CN110974718A CN 110974718 A CN110974718 A CN 110974718A CN 201911416355 A CN201911416355 A CN 201911416355A CN 110974718 A CN110974718 A CN 110974718A
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- 239000000843 powder Substances 0.000 title claims abstract description 166
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 59
- MVORZMQFXBLMHM-QWRGUYRKSA-N Gly-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 MVORZMQFXBLMHM-QWRGUYRKSA-N 0.000 claims abstract description 59
- 229910052802 copper Inorganic materials 0.000 claims abstract description 59
- 239000010949 copper Substances 0.000 claims abstract description 59
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims abstract description 57
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 claims abstract description 57
- 229960003237 betaine Drugs 0.000 claims abstract description 57
- 238000004108 freeze drying Methods 0.000 claims abstract description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 49
- 239000008367 deionised water Substances 0.000 claims abstract description 42
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 42
- 238000000034 method Methods 0.000 claims abstract description 22
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 19
- 239000003906 humectant Substances 0.000 claims abstract description 12
- 239000012452 mother liquor Substances 0.000 claims description 44
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 41
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 39
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 39
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 39
- 239000008176 lyophilized powder Substances 0.000 claims description 36
- 239000010413 mother solution Substances 0.000 claims description 35
- 238000011049 filling Methods 0.000 claims description 28
- 229930195725 Mannitol Natural products 0.000 claims description 24
- 239000000594 mannitol Substances 0.000 claims description 24
- 235000010355 mannitol Nutrition 0.000 claims description 24
- 238000001816 cooling Methods 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 10
- 229930182555 Penicillin Natural products 0.000 claims description 9
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 9
- 229940049954 penicillin Drugs 0.000 claims description 9
- 230000001954 sterilising effect Effects 0.000 claims description 8
- 239000001913 cellulose Substances 0.000 claims description 6
- 229920002678 cellulose Polymers 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 238000011146 sterile filtration Methods 0.000 claims description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- 238000012792 lyophilization process Methods 0.000 claims description 2
- 230000005012 migration Effects 0.000 abstract description 36
- 238000013508 migration Methods 0.000 abstract description 36
- 239000000126 substance Substances 0.000 abstract description 28
- 230000008569 process Effects 0.000 abstract description 16
- 239000002537 cosmetic Substances 0.000 abstract description 3
- 230000035699 permeability Effects 0.000 abstract description 3
- 239000003223 protective agent Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 230000000694 effects Effects 0.000 description 18
- 239000013543 active substance Substances 0.000 description 8
- 238000004659 sterilization and disinfection Methods 0.000 description 6
- 238000007710 freezing Methods 0.000 description 4
- 230000008014 freezing Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000007599 discharging Methods 0.000 description 3
- 230000005496 eutectics Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000530268 Lycaena heteronea Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 230000009477 glass transition Effects 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0216—Solid or semisolid forms
- A61K8/022—Powders; Compacted Powders
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
-
- 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
-
- 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
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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)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to freeze-dried powder and a preparation method thereof, belonging to the field of cosmetics. The freeze-dried powder provided by the invention comprises the following components in percentage by weight: tripeptide-1 copper 0.1-2%, humectant 0.2-7%, excipient 0.1-23% and deionized water the rest. According to the invention, betaine with low consistency is used as a protective agent for resisting solute migration, and the weight ratio of betaine to tripeptide-1 copper is 3:1, so that the prepared freeze-dried powder has no migration of colored substances, good stability, normal appearance and good re-solubility; the freeze-dried powder obtained after freeze-drying treatment has smooth and fine appearance, good reproducibility and good permeability; the freeze-dried powder prepared by the method has the advantages of low cost, cheap raw materials, simple process, no need of complex equipment, low requirement on occupational quality of operators, easy realization and industrial large-scale popularization and production.
Description
Technical Field
The invention relates to freeze-dried powder and a preparation method thereof, belonging to the field of cosmetics.
Background
The lyophilized powder is sterile powder prepared by ultralow temperature freezing process under vacuum condition, and is cosmetic with repairing effect. The preparation of the freeze-dried powder comprises the screening of a formula and the design of a freeze-drying process; the freeze-dried powder with good effect is often twice with half the effort, various abnormal phenomena in the freeze-drying process can be effectively reduced, and the appearance, re-dissolubility, moisture content, storage life and glass transition temperature of a freeze-dried finished product meet the industrial standard. The formula of the freeze-dried powder comprises an excipient and an active substance, and the proper excipient is selected according to the property of the active substance, so that the activity of the active substance can be maintained to the maximum extent, and meanwhile, the good appearance and other indexes such as re-solubility, water content and the like are maintained; the freeze-drying process of freeze-drying powder is characterized by that the screened proper formula is freeze-dried, before freeze-drying, sterile filtration is also conducted so as to ensure aseptic detection of freeze-drying powder, then the proper freeze-drying process curve is designed by means of measuring parameters of eutectic point, glass transition temperature, eutectic point and variety property of active matter, etc. to make freeze-drying.
For the phenomenon that colored freeze-dried powder containing bluecopper peptides and the like often generates color migration in the freezing process, the color of the bottom and the color of the upper layer of the colored freeze-dried powder are obviously different, the phenomenon that the upper layer is deeper and the lower layer is lighter is often shown, particularly when the color is darker, the phenomenon is obvious, most of the freeze-dried powder products sold in the market at present limit the migration of colored substances by adding thickening agents (such as carbomer, sodium hyaluronate, hydroxymethyl cellulose and the like) in the formula of the freeze-dried powder, namely limit the migration of the colored substances from the formula level. The migration of the colored substances is limited by improving the process, for example, the freeze-dried powder is solidified in a very short time by adopting a liquid nitrogen quick freezing method, so that the colored substances cannot migrate in time, the solution is kept uniform, and the problem in the process aspect is solved. These methods for solving the color migration in lyophilized powders all have significant drawbacks. From the aspect of a formula, the migration of pigments can be weakened by increasing the consistency, but the difficulty of aseptic filtration is increased by increasing the consistency, the aperture of the aseptic filtration is smaller, the speed of the aseptic filtration is greatly reduced by increasing the consistency, even the phenomenon that the filtration cannot be carried out occurs, the risk of bacterial contamination is reduced by adding a preservative or a high-temperature sterilization mode, the redissolution of freeze-dried powder is greatly influenced by increasing the consistency, and the redissolution of a product can be reduced by increasing the general consistency. The perfect uniform and fine freeze-dried powder can be obtained by fast freezing in the aspect of process, but the method has high operation difficulty, high equipment cost, higher requirement on personnel and high cost consumption in all aspects.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the freeze-dried powder which can solve the problem of color migration in the freeze-drying process of the bluecopper peptide freeze-dried powder and can keep good re-solubility, reproducibility, appearance characteristics and storage stability.
The invention also aims to provide a preparation method of the freeze-dried powder.
In order to achieve the purpose, the invention adopts the technical scheme that: the freeze-dried powder comprises the following components in percentage by weight: tripeptide-1 copper 0.1-2%, humectant 0.2-7%, excipient 0.1-23% and deionized water the rest.
Preferably, the humectant is betaine.
Betaine is a good humectant and can increase the expansion speed and the average consistency of a water-soluble polymer thickener, but pure betaine has no obvious influence on the consistency in aqueous solution, the betaine can form strong hydrogen bonds in the aqueous solution, hydrophilic groups in betaine molecules attract hydrogen atoms in water molecules but cannot be firmly combined, and hydrophobic methyl in the betaine generates repulsion force on the water molecules, so that the activity of water is changed, bottom ice crystals are formed at lower temperature and tend to reach lower temperature integrally, and then the ice crystals are quickly frozen near a eutectic point, so that the migration of solutes is not easily formed, and colored substances are uniformly and stably frozen into a solid state.
Preferably, the excipient is selected from at least one of mannitol, trehalose, lactose, sucrose, phosphate and glycine; more preferably, the excipients are mannitol and trehalose.
The excipient effect and the active matter protection effect of different excipients are different, and changing the types and the weight content of the excipients often has great influence on the appearance, the activity and the color depth of the freeze-dried powder. The excipient disclosed by the invention has a good protection effect on active substances in the freeze-dried powder in a reasonable weight content range through screening, and has no influence on migration of colored substances.
Preferably, the freeze-dried powder comprises the following components in percentage by weight: tripeptide-1 copper 0.1-2%, betaine 0.2-7%, mannitol 2-20%, trehalose 0.1-3% and the balance of deionized water.
Through a large number of experimental researches, the inventor of the application provides a formula of the freeze-dried powder, and the freeze-dried powder is freeze-dried by using the preparation method provided by the invention, the formula and the preparation method can well inhibit the migration of a colored substance tripeptide-1 copper, and the obtained freeze-dried powder has uniform color, good stability and good reproducibility.
Preferably, the weight ratio of betaine to tripeptide-1 copper is 3: 1.
In the formula of the freeze-dried powder, when the weight ratio of the betaine to the tripeptide-1 copper is 3:1, the freeze-dried powder is prepared into freeze-dried powder, the requirements on a freeze-drying process are low, the obtained freeze-dried powder is uniform in color and best in stability, and meanwhile, the freeze-dried powder has smooth and exquisite blocky appearance and active substances can be well protected.
The invention provides a preparation method of freeze-dried powder, which comprises the following steps:
(1) dissolving tripeptide-1 copper, an excipient and a humectant in deionized water according to a formula ratio, and fully and uniformly stirring to prepare a freeze-dried powder mother solution;
(2) sterilizing and filtering the freeze-dried powder mother liquor obtained in the step (1), filling the freeze-dried powder mother liquor into a container, and performing half plugging treatment on the container to obtain filled freeze-dried powder mother liquor;
(3) and (3) placing the filling freeze-dried powder mother solution in the step (2) on a plate layer of a freeze dryer for freeze-drying treatment in 7 stages to obtain the freeze-dried powder.
As a preferred embodiment of the preparation method of the present invention, in the step (2), the sterile filtration is performed by using a 0.22 micron mixed cellulose membrane or a filter element to perform sterile filtration on the freeze-dried powder mother liquor; the container is a washed and dried 3ml or 5ml penicillin bottle, and the height of the freeze-dried powder mother solution filled in the container is 10-15 mm.
As a preferred embodiment of the preparation method of the present invention, in the step (3), the 7-stage lyophilization processes specifically include: stage 1: reducing the temperature of the mother solution of the filled freeze-dried powder to-10 to-15 ℃ at a cooling speed of 1 to 10 ℃/min, and then keeping the temperature for 30 to 180 min; stage 2: reducing the temperature of the filling freeze-dried powder mother liquor in the first stage to-45-85 ℃ at a cooling speed of 1-5 ℃/min under normal pressure, and then keeping the temperature for 120-480 min; stage 3: under normal pressure, raising the temperature of the filling freeze-drying powder mother liquor which finishes the second stage to-20 to-30 ℃ at the temperature raising speed of 0.5-5/min, and then keeping the temperature for 300-600 min under the pressure of 10-13 pa; and 4, stage: raising the temperature of the filling freeze-drying powder mother liquor in the third stage to 0-3 ℃ at the temperature rise speed of 1-5 ℃/min, and then keeping the temperature for 300-600 min at the pressure of 18-21 pa; stage 5: raising the temperature of the filling freeze-drying powder mother liquor in the fourth stage to 10-16 ℃ at the temperature rise speed of 1-5 ℃/min, and then keeping the temperature at 23-26pa for 240-450 min; stage 6: raising the temperature of the mother solution of the filled freeze-dried powder in the fifth stage to 35-40 ℃ at a heating rate of 1-10 ℃/min, and then keeping the temperature at 28-32pa for 90-120 min; and 7, performing constant temperature and constant pressure on the filled freeze-dried powder mother liquor in the fifth stage for 120-280 min at the temperature of 35-40 ℃ and under the pressure of 1-5 pa, then plugging, breaking vacuum and taking out of the box, namely completing freeze-drying treatment.
According to the freeze-drying treatment, in the freeze-drying process, the freeze-dried powder mother liquor is generally subpackaged in the penicillin bottle and placed on the plate layer of the freeze-drying machine, and the freeze-dried powder mother liquor is frozen by refrigerating the plate layer, so that the freeze-dried powder mother liquor is rapidly cooled mainly by the direct contact heat transfer between the bottom of the penicillin bottle and the plate layer in the process, the bottom of the penicillin bottle and the upper layer have a large temperature difference, ice crystals grow from the bottom first, and other solutes including colored substances are forced to migrate from the bottom to the upper layer, so that large gradual change in color is formed after freeze-drying is finished.
Compared with the prior art, the invention has the beneficial effects that: according to the invention, betaine with low consistency is used as a protective agent for resisting solute migration, so that the prepared freeze-dried powder has good re-solubility, does not obviously influence the activity of active substances of the freeze-dried powder, does not increase the conductivity of an aqueous solution, and can be well formed; the freeze-dried powder obtained after freeze-drying treatment has smooth and fine appearance, good reproducibility, weak acidity, stability, no harm to skin and good moisture retention performance; the freeze-dried powder disclosed by the invention is good in permeability, has a certain sterilization and anti-inflammation effect, is low in cost, low in raw material price, simple in process, free of complex equipment and low in requirement on occupational quality of operators, is easy to prepare, and can be industrially popularized and produced in a large scale.
Detailed Description
To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to specific examples.
Example 1
The purpose of this example is to compare the effect of betaine addition on the migration of a coloured substance (tripeptide-1 copper) during lyophilization and other indicators
In this example, the migration condition, appearance and solubility of the colored substances were detected or observed for 3 kinds of lyophilized powders (nos. 2, 3 and 4) and a lyophilized powder (No. 1, control group) not containing betaine according to the present invention, and the solubility test was performed using physiological saline, and the results are shown in table 1.
The freeze-dried powder with the number 1 comprises the following components in percentage by weight: 1% of tripeptide-1 copper, 1% of trehalose, 8% of mannitol and 90% of deionized water.
The freeze-dried powder with the number 2 comprises the following components in percentage by weight: 1% of tripeptide-1 copper, 0.2% of betaine, 1% of trehalose, 8% of mannitol and 89.8% of deionized water.
The freeze-dried powder with the number 3 comprises the following components in percentage by weight: 1% of tripeptide-1 copper, 3% of betaine, 1% of trehalose, 8% of mannitol and 87% of deionized water.
The freeze-dried powder with the number 4 comprises the following components in percentage by weight: 1% of tripeptide-1 copper, 7% of betaine, 1% of trehalose, 8% of mannitol and 83% of deionized water.
The preparation method of the lyophilized powder with the number 2 comprises the following steps:
(1) dissolving tripeptide-1 copper, an excipient and a humectant in deionized water according to a formula ratio, and fully and uniformly stirring to prepare a freeze-dried powder mother solution;
(2) performing sterilization filtration on the freeze-dried powder mother liquor obtained in the step (1) by using a 0.22 micron mixed cellulose membrane or filter element; filling the mixture into a clean and dried 3ml penicillin bottle, wherein the height of the freeze-dried powder mother solution filled in the container is 10mm, and then performing half plugging treatment on the container to obtain filled freeze-dried powder mother solution;
(3) and (3) placing the filling freeze-dried powder mother solution in the step (2) on a plate layer of a freeze dryer for freeze-drying treatment in 7 stages to obtain the freeze-dried powder. Wherein the freeze-drying treatment of the 7 stages specifically comprises: stage 1: reducing the temperature of the mother solution of the filled freeze-dried powder to-15 ℃ at a cooling speed of 10 ℃/min, and then keeping the temperature for 30 min; stage 2: reducing the temperature of the filled freeze-dried powder mother liquor in the first stage to-45 ℃ at a cooling speed of 1 ℃/min under normal pressure, and then keeping the temperature for 120 min; stage 3: raising the temperature of the mother solution of the filled freeze-dried powder in the second stage to-20 ℃ at a heating rate of 0.5 ℃/min under normal pressure, and then keeping the temperature for 600min under the pressure of 10 pa; and 4, stage: raising the temperature of the filling freeze-drying powder mother liquor in the third stage to 0 ℃ at the temperature rise speed of 1 ℃/min, and then keeping the temperature for 300min under the pressure of 18 pa; stage 5: raising the temperature of the filling freeze-drying powder mother liquor in the fourth stage to 10 ℃ at the temperature rise speed of 1 ℃/min, and then keeping the temperature for 240min at the pressure of 23 pa; stage 6: raising the temperature of the mother solution of the filled freeze-drying powder in the fifth stage to 35 ℃ at the temperature rise speed of 1 ℃/min, and then keeping the temperature for 90min at the pressure of 28 pa; and 7, performing constant temperature and constant pressure 120min on the filled freeze-dried powder mother liquor in the fifth stage at the temperature of 35 ℃ and the pressure of 5pa, then plugging, breaking vacuum and then discharging from the box, namely completing freeze-drying treatment.
The preparation method of the lyophilized powder of the above numbers 1, 3 and 4 is the same as the preparation method of the lyophilized powder of the number 2.
TABLE 1 Effect of betaine addition on migration of colored substances during lyophilization and other indicators
As can be seen from table 1 above, it can be seen by comparing the control group with the lyophilized powder of the present invention that the migration of the colored substance is significantly reduced by the addition of betaine, but with the increase of the concentration, the solubility and the appearance are affected to some extent, and the higher the concentration of betaine is, the better the inhibition effect on the migration of the colored substance is, and when the weight ratio of betaine to tripeptide-1 copper is 3:1, the colored substance does not migrate, and the appearance and the re-solubility are the best.
Example 2
The purpose of this example is to compare the concentration of different mannitol in lyophilized powder and to determine the effect of color migration, appearance and solubility of the lyophilized powder
In this example, the migration condition, appearance and solubility of the colored substances were detected or observed for 3 kinds of lyophilized powders (nos. 2, 3 and 4) and 2 kinds of lyophilized powders (nos. 1 and 5) of the control group, and the solubility test was performed using physiological saline, and the results are shown in table 2.
The freeze-dried powder with the number 1 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1%, trehalose 0.5%, mannitol 1%, and deionized water 97%.
The freeze-dried powder with the number 2 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1%, trehalose 0.5%, mannitol 2%, and deionized water 96%.
The freeze-dried powder with the number 3 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1%, trehalose 0.5%, mannitol 10%, deionized water 88%.
The freeze-dried powder with the number 4 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1%, trehalose 0.5%, mannitol 20%, and deionized water 78%.
The freeze-dried powder with the number 5 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1%, trehalose 0.5%, mannitol 30%, and deionized water 68%.
The preparation method of the lyophilized powder with the number 2 comprises the following steps:
(1) dissolving tripeptide-1 copper, an excipient and a humectant in deionized water according to a formula ratio, and fully and uniformly stirring to prepare a freeze-dried powder mother solution;
(2) performing sterilization filtration on the freeze-dried powder mother liquor obtained in the step (1) by using a 0.22 micron mixed cellulose membrane or filter element; filling the mixture into a clean and dried 3ml penicillin bottle, wherein the height of the freeze-dried powder mother solution filled in the container is 15mm, and then performing half plugging treatment on the container to obtain filled freeze-dried powder mother solution;
(3) and (3) placing the filling freeze-dried powder mother solution in the step (2) on a plate layer of a freeze dryer for freeze-drying treatment in 7 stages to obtain the freeze-dried powder. Wherein the freeze-drying treatment of the 7 stages specifically comprises: stage 1: reducing the temperature of the mother solution of the filled freeze-dried powder to-15 ℃ at a cooling speed of 10 ℃/min, and then keeping the temperature for 30 min; stage 2: reducing the temperature of the filled freeze-dried powder mother liquor in the first stage to-45 ℃ at a cooling speed of 1 ℃/min under normal pressure, and then keeping the temperature for 120 min; stage 3: raising the temperature of the mother solution of the filled freeze-dried powder in the second stage to-20 ℃ at a heating rate of 0.5 ℃/min under normal pressure, and then keeping the temperature for 600min under the pressure of 13 pa; and 4, stage: raising the temperature of the filling freeze-drying powder mother liquor in the third stage to 0 ℃ at the temperature rise speed of 1 ℃/min, and then keeping the temperature for 300min at the pressure of 21 pa; stage 5: raising the temperature of the filling freeze-drying powder mother liquor in the fourth stage to 10 ℃ at the temperature rise speed of 1 ℃/min, and then keeping the temperature for 240min under the pressure of 26 pa; stage 6: raising the temperature of the mother solution of the filled freeze-drying powder in the fifth stage to 35 ℃ at the temperature rise speed of 1 ℃/min, and then keeping the temperature for 90min under the pressure of 32 pa; and 7, performing constant temperature and constant pressure 120min on the filled freeze-dried powder mother liquor in the fifth stage at the temperature of 35 ℃ and the pressure of 5pa, then plugging, breaking vacuum and then discharging from the box, namely completing freeze-drying treatment.
The preparation method of the lyophilized powder of the above numbers 1, 3, 4 and 5 is the same as the preparation method of the lyophilized powder of the number 2.
TABLE 2 Effect of different mannitol levels in lyophilized powder on color migration and other indicators
As can be seen from table 2, comparison of the control group with the lyophilized powder of the present invention revealed that the lyophilized powder was difficult to form, i.e., abnormal in appearance, at a lower mannitol concentration; when the concentration of mannitol is higher, the influence on redissolution is larger, namely the redissolution performance is poor, but the concentration of mannitol has no obvious influence on the migration condition of the colored substance tripeptide-1 copper, and the weight content of mannitol in the freeze-dried powder is 2-20%.
Example 3
The purpose of this example is to compare the effect of trehalose addition and the concentration of the tripeptide-1 copper itself on the migration of the coloured substance tripeptide-1 copper,
in this example, the migration condition, appearance and re-solubility of the colored substances of 7 kinds of lyophilized powders (nos. 1-7) and 2 kinds of lyophilized powders (No. 8) of the control group according to the present invention were tested or observed, and the results of the dissolution test using physiological saline were shown in table 3.
The freeze-dried powder with the number 1 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1%, trehalose 0.1%, mannitol 5%, and deionized water 93.4%.
The freeze-dried powder with the number 2 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1%, trehalose 0.8%, mannitol 5%, deionized water 92.7%.
The freeze-dried powder with the number 3 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1%, trehalose 2.4%, mannitol 5%, deionized water 91.1%.
The freeze-dried powder with the number 4 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1%, trehalose 3%, mannitol 5%, deionized water 90.5%.
The freeze-dried powder with the number 5 comprises the following components in percentage by weight: tripeptide-1 copper 0.1%, betaine 1%, trehalose 0.5%, mannitol 5%, and deionized water 93.4%.
The freeze-dried powder with the number 6 comprises the following components in percentage by weight: 1% of tripeptide-1 copper, 1% of betaine, 0.5% of trehalose, 5% of mannitol and 92.5% of deionized water.
The freeze-dried powder with the number 7 comprises the following components in percentage by weight: tripeptide-1 copper 2%, betaine 1%, trehalose 0.5%, mannitol 5%, and deionized water 91.5%.
The freeze-dried powder with the number 8 comprises the following components in percentage by weight: tripeptide-1 copper 3%, betaine 1%, trehalose 0.5%, mannitol 5%, and deionized water 90.5%.
The preparation method of the lyophilized powder of the above No. 1-8 is the same as that of the lyophilized powder of the No. 2 of the example 1.
TABLE 3 influence of trehalose and tripeptide-1 copper by weight on migration of coloured substances and other indicators of lyophilized powder
In the above table 3, the comparison of the lyophilized powders numbered 1-4 shows that the concentration of trehalose does not have obvious influence on the migration condition, appearance and re-solubility of the colored substances of the lyophilized powders, and the addition of trehalose in the lyophilized powders mainly aims at protecting the activity of the active substances and increasing the moisture retention of the product without considering the influence on the appearance. The comparison of numbers 5-7 with the control number 8 shows that the weight content of copper, the tripeptide-1, which is a colored substance, does not affect the color migration. Tripeptide-1 copper in the freeze-dried powder is a main active substance, the concentration is too low, the color is not obvious, the color migration is difficult to judge, the cost is high due to too high concentration, the market requirement is not met, and the color migration is difficult to judge due to too deep color.
Example 4
This example mainly explores the effect of the optimal weight ratio of betaine and tripeptide-1 copper on migration of colored substances in lyophilized powder
In this example, the migration condition, appearance and re-solubility of the colored substances of 12 kinds of freeze-dried powders (numbers 1-12) of the present invention were detected or observed, and the results of the dissolution test using physiological saline were shown in table 4.
The freeze-dried powder with the number 1 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1%, trehalose 0.1%, mannitol 5%, and deionized water 93.4%.
The freeze-dried powder with the number 2 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1.2%, trehalose 0.8%, mannitol 5%, deionized water 92.5%.
The freeze-dried powder with the number 3 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1.5%, trehalose 2.4%, mannitol 5%, deionized water 90.6%.
The freeze-dried powder with the number 4 comprises the following components in percentage by weight: tripeptide-1 copper 0.5%, betaine 1.8%, trehalose 3%, mannitol 5%, deionized water 89.7%.
The freeze-dried powder with the number 5 comprises the following components in percentage by weight: 1% of tripeptide-1 copper, 2.5% of betaine, 0.5% of trehalose, 5% of mannitol and 91% of deionized water.
The freeze-dried powder with the number 6 comprises the following components in percentage by weight: 1% of tripeptide-1 copper, 2.8% of betaine, 0.5% of trehalose, 5% of mannitol and 90.7% of deionized water.
The freeze-dried powder with the number 7 comprises the following components in percentage by weight: 1% of tripeptide-1 copper, 3.0% of betaine, 0.5% of trehalose, 5% of mannitol and 90.7% of deionized water.
The freeze-dried powder with the number 8 comprises the following components in percentage by weight: 1% of tripeptide-1 copper, 3.3% of betaine, 0.5% of trehalose, 5% of mannitol and 90.2% of deionized water.
The freeze-dried powder with the number 9 comprises the following components in percentage by weight: tripeptide-1 copper 2%, betaine 5.4%, trehalose 0.5%, mannitol 5%, and deionized water 87.1%.
The freeze-dried powder with the number 10 comprises the following components in percentage by weight: tripeptide-1 copper 2%, betaine 5.8%, trehalose 0.5%, mannitol 5%, and deionized water 86.7%.
The freeze-dried powder with the number 11 comprises the following components in percentage by weight: tripeptide-1 copper 2%, betaine 6.0%, trehalose 0.5%, mannitol 5%, and deionized water 86.5%.
The freeze-dried powder with the number 12 comprises the following components in percentage by weight: tripeptide-1 copper 2%, betaine 6.5%, trehalose 0.5%, mannitol 5% and deionized water 86%.
The preparation method of the lyophilized powder of the above No. 1-12 is the same as that of the lyophilized powder of the No. 2 of the example 2.
TABLE 4 influence of weight ratio of betaine and tripeptide-1 copper on migration of colored substances and other indicators of lyophilized powder
From the results in table 4 above, it can be seen that the addition of betaine at a certain concentration can effectively inhibit the migration of the colored substances, but when the ratio of betaine to tripeptide-1 copper is close to 3:1, the migration of the colored substances in the lyophilized powder is minimal, the appearance is normal, and the redissolution is very soluble.
Example 5
The embodiment is a freeze-dried powder, which comprises the following components in percentage by weight: tripeptide-1 copper 0.1%, betaine 0.3%, lactose 6%, phosphate 17%, deionized water 76.6%.
The preparation method of the freeze-dried powder comprises the following steps:
(1) dissolving tripeptide-1 copper, an excipient and a humectant in deionized water according to a formula ratio, and fully and uniformly stirring to prepare a freeze-dried powder mother solution;
(2) performing sterilization filtration on the freeze-dried powder mother liquor obtained in the step (1) by using a 0.22 micron mixed cellulose membrane or filter element; filling the mixture into a clean and dried 5ml penicillin bottle, wherein the height of the freeze-dried powder mother liquor filled in the container is 12mm, and then performing half plugging treatment on the container to obtain filled freeze-dried powder mother liquor;
(3) and (3) placing the filling freeze-dried powder mother solution in the step (2) on a plate layer of a freeze dryer for freeze-drying treatment in 7 stages to obtain the freeze-dried powder. Wherein the freeze-drying treatment of the 7 stages specifically comprises: stage 1: reducing the temperature of the mother solution of the filled freeze-dried powder to-10 ℃ at the cooling speed of 1 ℃/min, and then keeping the temperature for 180 min; stage 2: reducing the temperature of the mother solution of the filled freeze-dried powder in the first stage to-85 ℃ at a cooling speed of 5 ℃/min under normal pressure, and then keeping the temperature for 480 min; stage 3: raising the temperature of the mother solution of the filled freeze-dried powder in the second stage to-30 ℃ at the temperature rise speed of 5 ℃/min under normal pressure, and then keeping the temperature for 300min under the pressure of 10 pa; and 4, stage: raising the temperature of the filling freeze-drying powder mother liquor in the third stage to 3 ℃ at the temperature rise speed of 5 ℃/min, and then keeping the temperature for 600min under the pressure of 18 pa; stage 5: raising the temperature of the filling freeze-drying powder mother liquor in the fourth stage to 16 ℃ at the temperature rise speed of 5 ℃/min, and then keeping the temperature for 450min at the pressure of 23 pa; stage 6: raising the temperature of the mother solution of the filled freeze-drying powder in the fifth stage to 40 ℃ at a heating rate of 10 ℃/min, and then keeping the temperature for 120min at the pressure of 28 pa; and 7, keeping the filled freeze-dried powder mother liquor in the fifth stage at the temperature of 40 ℃ and the pressure of 1pa for 280min at constant temperature and constant pressure, then plugging, breaking vacuum and then discharging from the box, namely, completing freeze-drying treatment.
Example 6
The embodiment is a freeze-dried powder, which comprises the following components in percentage by weight: tripeptide-1 copper 2%, betaine 6%, sucrose 0.1%, glycine 0.1%, and deionized water 91.8%.
The preparation method of the freeze-dried powder comprises the following steps:
(1) dissolving tripeptide-1 copper, an excipient and a humectant in deionized water according to a formula ratio, and fully and uniformly stirring to prepare a freeze-dried powder mother solution;
(2) performing sterilization filtration on the freeze-dried powder mother liquor obtained in the step (1) by using a 0.22 micron mixed cellulose membrane or filter element; filling the mixture into a clean and dried 4ml penicillin bottle, wherein the height of the freeze-dried powder mother liquor filled in the container is 12mm, and then performing half plugging treatment on the container to obtain filled freeze-dried powder mother liquor;
(3) and (3) placing the filling freeze-dried powder mother solution in the step (2) on a plate layer of a freeze dryer for freeze-drying treatment in 7 stages to obtain the freeze-dried powder. Wherein the freeze-drying treatment of the 7 stages specifically comprises: stage 1: reducing the temperature of the mother solution of the filled freeze-dried powder to-15 ℃ at the cooling speed of 8 ℃/min, and then keeping the temperature for 100 min; stage 2: reducing the temperature of the filled freeze-dried powder mother liquor in the first stage to-65 ℃ at a cooling speed of 3 ℃/min under normal pressure, and then keeping the temperature for 200 min;
stage 3: raising the temperature of the mother solution of the filled freeze-dried powder in the second stage to-25 ℃ at the temperature rise speed of 5 ℃/min under normal pressure, and then keeping the temperature for 400min under the pressure of 10 pa; and 4, stage: raising the temperature of the filling freeze-drying powder mother liquor in the third stage to 3 ℃ at the temperature rise speed of 3 ℃/min, and then keeping the temperature for 400min at the pressure of 21 pa; stage 5: raising the temperature of the filling freeze-drying powder mother liquor in the fourth stage to 13 ℃ at the temperature rise speed of 4 ℃/min, and then keeping the temperature for 300min at the pressure of 23 pa; stage 6: raising the temperature of the mother solution of the filled freeze-drying powder in the fifth stage to 38 ℃ at the temperature rise speed of 8 ℃/min, and then keeping the temperature for 100min under the pressure of 32 pa; and 7, keeping the temperature and the pressure of the filled freeze-dried powder mother liquor in the fifth stage at 38 ℃ and 4pa for 160min at constant temperature and constant pressure, then plugging, breaking vacuum and taking out of the box, namely completing freeze-drying treatment.
In conclusion, the invention adopts the betaine with lower consistency as a protective agent for resisting solute migration, and the weight ratio of the betaine to the tripeptide-1 copper is 3:1, so that the prepared freeze-dried powder has no migration of colored substances, good stability, normal appearance and very good re-solubility; the freeze-dried powder obtained after freeze-drying treatment has smooth and fine appearance, good reproducibility and good permeability; the freeze-dried powder prepared by the method has the advantages of low cost, cheap raw materials, simple process, no need of complex equipment, low requirement on occupational quality of operators, easy realization and industrial large-scale popularization and production.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (8)
1. The freeze-dried powder is characterized by comprising the following components in percentage by weight: tripeptide-1 copper 0.1-2%, humectant 0.2-7%, excipient 0.1-23% and deionized water the rest.
2. Lyophilized powder according to claim 1, wherein the humectant is betaine; the excipient is at least one of mannitol, trehalose, lactose, sucrose, phosphate and glycine.
3. Lyophilized powder according to claim 2, wherein the excipients are mannitol and trehalose.
4. The lyophilized powder of claim 3, comprising the following components in weight percent: tripeptide-1 copper 0.1-2%, betaine 0.2-7%, mannitol 2-20%, trehalose 0.1-3% and the balance of deionized water.
5. Lyophilized powder according to claim 4, wherein the weight ratio of betaine to tripeptide-1 copper is 3: 1.
6. A method of preparing a lyophilized powder according to any one of claims 1-5, comprising the steps of:
(1) dissolving tripeptide-1 copper, an excipient and a humectant in deionized water according to a formula ratio, and fully and uniformly stirring to prepare a freeze-dried powder mother solution;
(2) sterilizing and filtering the freeze-dried powder mother liquor obtained in the step (1), filling the freeze-dried powder mother liquor into a container, and performing half plugging treatment on the container to obtain filled freeze-dried powder mother liquor;
(3) and (3) placing the filling freeze-dried powder mother solution in the step (2) on a plate layer of a freeze dryer for freeze-drying treatment in 7 stages to obtain the freeze-dried powder.
7. The preparation method according to claim 6, wherein in the step (2), the sterile filtration is performed by using a 0.22 micron mixed cellulose membrane or a filter element to perform sterile filtration on the freeze-dried powder mother liquor; the container is a washed and dried 3ml or 5ml penicillin bottle, and the height of the freeze-dried powder mother solution filled in the container is 10-15 mm.
8. The preparation method according to claim 6, wherein in the step (3), the 7-stage lyophilization processes are specifically: stage 1: reducing the temperature of the mother solution of the filled freeze-dried powder to-10 to-15 ℃ at a cooling speed of 1 to 10 ℃/min, and then keeping the temperature for 30 to 180 min; stage 2: reducing the temperature of the filling freeze-dried powder mother liquor in the first stage to-45-85 ℃ at a cooling speed of 1-5 ℃/min under normal pressure, and then keeping the temperature for 120-480 min; stage 3: under normal pressure, raising the temperature of the filling freeze-drying powder mother liquor which finishes the second stage to-20 to-30 ℃ at the temperature raising speed of 0.5-5/min, and then keeping the temperature for 300-600 min under the pressure of 10-13 pa; and 4, stage: raising the temperature of the filling freeze-drying powder mother liquor in the third stage to 0-3 ℃ at the temperature rise speed of 1-5 ℃/min, and then keeping the temperature for 300-600 min at the pressure of 18-21 pa; stage 5: raising the temperature of the filling freeze-drying powder mother liquor in the fourth stage to 10-16 ℃ at the temperature rise speed of 1-5 ℃/min, and then keeping the temperature at 23-26pa for 240-450 min; stage 6: raising the temperature of the mother solution of the filled freeze-dried powder in the fifth stage to 35-40 ℃ at a heating rate of 1-10 ℃/min, and then keeping the temperature at 28-32pa for 90-120 min; and 7, performing constant temperature and constant pressure on the filled freeze-dried powder mother liquor in the fifth stage for 120-280 min at the temperature of 35-40 ℃ and under the pressure of 1-5 pa, then plugging, breaking vacuum and taking out of the box, namely completing freeze-drying treatment.
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| CN112263505A (en) * | 2020-10-29 | 2021-01-26 | 广州栋方生物科技股份有限公司 | Copper peptide composition and preparation method and application thereof |
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| CN107375004A (en) * | 2017-07-20 | 2017-11-24 | 房俊英 | A kind of colored lyophilized powder producing method |
| CN109512697A (en) * | 2019-01-04 | 2019-03-26 | 广州常青藤化妆品有限公司 | A kind of double-colored freeze-dried powder of Cocktail Method and preparation method thereof |
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| CN107375004A (en) * | 2017-07-20 | 2017-11-24 | 房俊英 | A kind of colored lyophilized powder producing method |
| CN109512697A (en) * | 2019-01-04 | 2019-03-26 | 广州常青藤化妆品有限公司 | A kind of double-colored freeze-dried powder of Cocktail Method and preparation method thereof |
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| CN111671666A (en) * | 2020-06-23 | 2020-09-18 | 湖南美媛本草生物工程有限公司 | Preparation method and application of freeze-dried powder containing multi-effect restoration composition |
| CN112263505A (en) * | 2020-10-29 | 2021-01-26 | 广州栋方生物科技股份有限公司 | Copper peptide composition and preparation method and application thereof |
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Effective date of registration: 20240425 Address after: Room 801, No. 7 Hexian North Street, Helong Street, Baiyun District, Guangzhou City, Guangdong Province, 510000 Patentee after: Aoya Cosmetics Research and Development (Guangzhou) Co.,Ltd. Country or region after: China Address before: 510000 4th floor, building B, No. 3, gangpu Avenue, Nanling, Taihe Town, Baiyun District, Guangzhou, Guangdong Patentee before: GUANGZHOU ATHENA COSMETICS MANUFACTURING CO.,LTD. Country or region before: China |