CN114681357B - Pre-preparation liquid of freeze-dried preparation containing grease, freeze-dried preparation and preparation method thereof - Google Patents
Pre-preparation liquid of freeze-dried preparation containing grease, freeze-dried preparation and preparation method thereof Download PDFInfo
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- CN114681357B CN114681357B CN202011623001.3A CN202011623001A CN114681357B CN 114681357 B CN114681357 B CN 114681357B CN 202011623001 A CN202011623001 A CN 202011623001A CN 114681357 B CN114681357 B CN 114681357B
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- Prior art keywords
- freeze
- preparation
- caprylic
- formulation
- polyethylene glycol
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- 238000002360 preparation method Methods 0.000 title claims abstract description 142
- 239000007788 liquid Substances 0.000 title claims abstract description 52
- 239000004519 grease Substances 0.000 title claims abstract description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 83
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 49
- 239000007957 coemulsifier Substances 0.000 claims abstract description 9
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 77
- 239000004698 Polyethylene Substances 0.000 claims description 74
- -1 polyethylene Polymers 0.000 claims description 74
- 229920000573 polyethylene Polymers 0.000 claims description 74
- 239000000203 mixture Substances 0.000 claims description 49
- 125000005456 glyceride group Chemical group 0.000 claims description 43
- 238000009472 formulation Methods 0.000 claims description 38
- 239000012071 phase Substances 0.000 claims description 38
- 239000002994 raw material Substances 0.000 claims description 34
- 239000003921 oil Substances 0.000 claims description 32
- 238000010438 heat treatment Methods 0.000 claims description 29
- 239000000654 additive Substances 0.000 claims description 27
- 230000000996 additive effect Effects 0.000 claims description 25
- 239000002245 particle Substances 0.000 claims description 22
- 239000012931 lyophilized formulation Substances 0.000 claims description 21
- BANXPJUEBPWEOT-UHFFFAOYSA-N 2-methyl-Pentadecane Chemical compound CCCCCCCCCCCCCC(C)C BANXPJUEBPWEOT-UHFFFAOYSA-N 0.000 claims description 20
- 238000004108 freeze drying Methods 0.000 claims description 20
- 238000004382 potting Methods 0.000 claims description 20
- NKJOXAZJBOMXID-UHFFFAOYSA-N 1,1'-Oxybisoctane Chemical group CCCCCCCCOCCCCCCCC NKJOXAZJBOMXID-UHFFFAOYSA-N 0.000 claims description 18
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 239000011230 binding agent Substances 0.000 claims description 14
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 14
- 238000001816 cooling Methods 0.000 claims description 14
- 239000004480 active ingredient Substances 0.000 claims description 13
- 239000003945 anionic surfactant Substances 0.000 claims description 13
- 239000004530 micro-emulsion Substances 0.000 claims description 13
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 12
- 239000000047 product Substances 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 11
- 229940043268 2,2,4,4,6,8,8-heptamethylnonane Drugs 0.000 claims description 10
- OQILCOQZDHPEAZ-UHFFFAOYSA-N Palmitinsaeure-octylester Natural products CCCCCCCCCCCCCCCC(=O)OCCCCCCCC OQILCOQZDHPEAZ-UHFFFAOYSA-N 0.000 claims description 10
- GJQLBGWSDGMZKM-UHFFFAOYSA-N ethylhexyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(CC)CCCCC GJQLBGWSDGMZKM-UHFFFAOYSA-N 0.000 claims description 10
- 229920006007 hydrogenated polyisobutylene Polymers 0.000 claims description 10
- KUVMKLCGXIYSNH-UHFFFAOYSA-N isopentadecane Natural products CCCCCCCCCCCCC(C)C KUVMKLCGXIYSNH-UHFFFAOYSA-N 0.000 claims description 10
- 235000010446 mineral oil Nutrition 0.000 claims description 10
- 239000002480 mineral oil Substances 0.000 claims description 10
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims description 9
- 150000003626 triacylglycerols Chemical class 0.000 claims description 9
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 229940079988 potassium cocoyl glycinate Drugs 0.000 claims description 8
- 239000011265 semifinished product Substances 0.000 claims description 8
- 229930003799 tocopherol Natural products 0.000 claims description 8
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- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 8
- 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 7
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 claims description 7
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 claims description 7
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 7
- 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 7
- 239000004386 Erythritol Substances 0.000 claims description 7
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims description 7
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 7
- 229930195725 Mannitol Natural products 0.000 claims description 7
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims description 7
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 claims description 7
- 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 7
- 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 7
- 235000013793 astaxanthin Nutrition 0.000 claims description 7
- 239000001168 astaxanthin Substances 0.000 claims description 7
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 claims description 7
- 229940022405 astaxanthin Drugs 0.000 claims description 7
- 229960001948 caffeine Drugs 0.000 claims description 7
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 7
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 claims description 7
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims description 7
- 235000019414 erythritol Nutrition 0.000 claims description 7
- 229940009714 erythritol Drugs 0.000 claims description 7
- 239000000594 mannitol Substances 0.000 claims description 7
- 235000010355 mannitol Nutrition 0.000 claims description 7
- 229940044591 methyl glucose dioleate Drugs 0.000 claims description 7
- 229960002446 octanoic acid Drugs 0.000 claims description 7
- 239000003223 protective agent Substances 0.000 claims description 7
- 235000021283 resveratrol Nutrition 0.000 claims description 7
- 229940016667 resveratrol Drugs 0.000 claims description 7
- 108700004121 sarkosyl Proteins 0.000 claims description 7
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 claims description 7
- 229940045885 sodium lauroyl sarcosinate Drugs 0.000 claims description 7
- 239000000600 sorbitol Substances 0.000 claims description 7
- 239000000230 xanthan gum Substances 0.000 claims description 7
- 229920001285 xanthan gum Polymers 0.000 claims description 7
- 229940082509 xanthan gum Drugs 0.000 claims description 7
- 235000010493 xanthan gum Nutrition 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 229940079779 disodium cocoyl glutamate Drugs 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- SHZIWNPUGXLXDT-UHFFFAOYSA-N ethyl hexanoate Chemical compound CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 claims description 6
- 238000007710 freezing Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 230000008014 freezing Effects 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 4
- 229920000057 Mannan Polymers 0.000 claims description 4
- 239000003974 emollient agent Substances 0.000 claims description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims description 4
- 150000004676 glycans Chemical class 0.000 claims description 4
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- 229920001282 polysaccharide Polymers 0.000 claims description 4
- 239000005017 polysaccharide Substances 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 230000002335 preservative effect Effects 0.000 claims description 4
- 229940045898 sodium stearoyl glutamate Drugs 0.000 claims description 4
- KDHFCTLPQJQDQI-BDQAORGHSA-M sodium;(4s)-4-amino-5-octadecanoyloxy-5-oxopentanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC(=O)[C@@H](N)CCC([O-])=O KDHFCTLPQJQDQI-BDQAORGHSA-M 0.000 claims description 4
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 239000008346 aqueous phase Substances 0.000 claims description 3
- PKPOVTYZGGYDIJ-UHFFFAOYSA-N dioctyl carbonate Chemical compound CCCCCCCCOC(=O)OCCCCCCCC PKPOVTYZGGYDIJ-UHFFFAOYSA-N 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 claims description 3
- 239000011159 matrix material Substances 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- LWBVAHQZGAKXPU-BOXHHOBZSA-M sodium;(4s)-4-amino-5-octadecoxy-5-oxopentanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOC(=O)[C@@H](N)CCC([O-])=O LWBVAHQZGAKXPU-BOXHHOBZSA-M 0.000 claims description 3
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- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims description 2
- AJLNZWYOJAWBCR-OOPVGHQCSA-N (4s)-4-acetamido-5-[[(2s)-1-[[(2s)-1-[[(2s)-5-amino-1-[[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-car Chemical compound OC(=O)CC[C@H](NC(C)=O)C(=C)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(N)=O AJLNZWYOJAWBCR-OOPVGHQCSA-N 0.000 claims description 2
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- 239000004359 castor oil Substances 0.000 description 2
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- 229920006037 cross link polymer Polymers 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 150000003077 polyols Chemical group 0.000 description 2
- 229940065859 sodium cocoyl glycinate Drugs 0.000 description 2
- IKGKWKGYFJBGQJ-UHFFFAOYSA-M sodium;2-(dodecanoylamino)acetate Chemical compound [Na+].CCCCCCCCCCCC(=O)NCC([O-])=O IKGKWKGYFJBGQJ-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 1
- RMTFNDVZYPHUEF-XZBKPIIZSA-N 3-O-methyl-D-glucose Chemical compound O=C[C@H](O)[C@@H](OC)[C@H](O)[C@H](O)CO RMTFNDVZYPHUEF-XZBKPIIZSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
Classifications
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- A61K2800/84—Products or compounds obtained by lyophilisation, freeze-drying
Abstract
The invention discloses a pre-preparation liquid of a freeze-dried preparation containing grease, the freeze-dried preparation and a preparation method thereof. The pre-preparation liquid of the freeze-dried preparation comprises the following components in percentage by weight: 6.0 to 12 percent of main emulsifier, 3.0 to 7.0 percent of auxiliary emulsifier, 5.0 to 9.0 percent of grease and water, wherein the sum of the weight percentages of the components is 100 percent; wherein the main emulsifier has a hydrophilic-lipophilic balance value of 11 or less; the coemulsifier has a hydrophilic-lipophilic balance of 12.5 or more. The freeze-dried preparation prepared by the pre-preparation liquid of the freeze-dried preparation has good water solubility, and the freeze-dried essence obtained after the freeze-dried preparation is dissolved can not undergo oil-water delamination and has good stability.
Description
Technical Field
The invention relates to a pre-preparation liquid of a freeze-dried preparation containing grease, a freeze-dried preparation and a preparation method thereof.
Background
The freeze-drying technology is a technology of freezing moisture in a material into ice, then heating the ice in the material under vacuum condition to enable ice crystals in the material to sublimate and resolve directly into water vapor, and removing the moisture in the material by capturing the water vapor in a system, so that the material can be dried, and a preparation prepared by the freeze-drying technology is called a freeze-dried preparation. The preparation adopts a freeze drying process, does not need to add any preservative, can protect heat sensitive components from being damaged, can avoid denaturation during storage and logistics transportation, and simultaneously generates a large number of micropores and pore channels through water sublimation, and can have very fast disintegration and dissolution speeds, thus being widely applied to a plurality of fields such as food, health-care food, medicines, daily chemicals, cosmetics and the like.
The freeze-dried preparation in the current cosmetic field mainly comprises a skeleton supporting agent, a binder and active ingredients, and often does not contain active grease and other emollients. The active grease is widely applied and very important in the field of cosmetics, not only provides moisture, softness and glossiness for skin, but also can inhibit the dryness of the skin and the evaporation of moisture on the surface of the skin in cold, and reduce the percutaneous water loss rate; can also be used as solvent for special components to dissolve liposoluble functional components such as vitamin A, tocopherol and its derivatives to promote absorption of nutritional components. One of the main reasons why the freeze-dried preparation in the market does not contain grease and other emollients at present is that various stresses can be generated in the freeze-drying process, and the stresses can damage the colloid structure in an emulsifying system, so that oil phases are separated, and the quality and the service performance of the freeze-dried preparation are seriously affected.
Disclosure of Invention
The invention provides a pre-preparation liquid of a freeze-dried preparation containing grease, a freeze-dried preparation and a preparation method thereof, aiming at solving the problems that the prepared freeze-dried essence can be subjected to oil-water delamination and has poor stability if the freeze-dried preparation contains grease and other oily components in the prior art. The freeze-dried preparation prepared by the pre-preparation liquid of the freeze-dried preparation has good water solubility, and the freeze-dried essence obtained after the freeze-dried preparation is dissolved can not undergo oil-water delamination and has good stability.
The invention solves the technical problems through the following technical proposal.
The invention provides a freeze-dried preparation pre-preparation liquid containing grease, which comprises the following components in percentage by weight: 6.0 to 12 percent of main emulsifier, 3.0 to 7.0 percent of auxiliary emulsifier, 5.0 to 9.0 percent of grease and water, wherein the sum of the weight percentages of the components is 100 percent;
wherein the main emulsifier has a hydrophilic-lipophilic balance value of 11 or less; the coemulsifier has a hydrophilic-lipophilic balance of 12.5 or more.
In the present invention, preferably, the pre-formulation of the lyophilized formulation is transparent or translucent in appearance.
In the present invention, the particle size of the pre-formulation of the lyophilized formulation is preferably less than 500nm, more preferably less than 250nm.
In the present invention, the main emulsifier preferably has a hydrophilic-lipophilic balance of 9 to 11, for example, 10.2.
In the present invention, the main emulsifier is preferably a nonionic emulsifier.
In the present invention, the main emulsifier is preferably an alkyl chain lipophilic surfactant having a structure containing 8 to 22 carbon atoms. The alkyl chain lipophilic group with the carbon number of 8-22 can be straight chain or branched chain, and can also be saturated carbon chain or unsaturated carbon chain. More preferably, the alkyl chain lipophilic group having 8 to 22 carbon atoms contains at least one branched chain. More preferably, the primary emulsifier is polyglycerol-6 dicaprate.
In the present invention, the content of the main emulsifier is preferably 7.0 to 10.0%, for example, 7%, 9% or 10%.
In the present invention, the coemulsifier preferably has a hydrophilic-lipophilic balance of 12.5 to 14, for example 13.2, 13.5 or 14.
In the present invention, the co-emulsifier is preferably a nonionic emulsifier.
In the present invention, preferably, the auxiliary emulsifier contains a lipophilic group and a hydrophilic group, and the hydrophilic group is a polyethylene glycol group or a polyol group, etc.; the polyol group is, for example, a glyceryl group, a sorbitol group, or the like. More preferably, the auxiliary emulsifier is one or more of polyethylene glycol-6 caprylic/capric glycerides, polyethylene glycol-7 caprylic/capric glycerides and polyethylene glycol-8 caprylic/capric glycerides, and even more preferably polyethylene glycol-6 caprylic/capric glycerides, polyethylene glycol-7 caprylic/capric glycerides or polyethylene glycol-8 caprylic/capric glycerides.
In the present invention, the content of the co-emulsifier is preferably 5.0 to 7.0%, for example, 6% or 7%.
In the present invention, the oil is preferably one or more of alkanes, ethers, esters and triglycerides.
Wherein the alkane is preferably one or more of mineral oil, isohexadecane and hydrogenated polyisobutene.
Wherein the ether is preferably dioctyl ether.
Wherein the esters are preferably one or more of dioctyl carbonate, isopropyl myristate, isopropyl palmitate and ethylhexyl palmitate.
Wherein the triglycerides are preferably one or more of tri (ethylhexanoate) and caprylic/capric triglyceride.
In a preferred embodiment, the grease is hydrogenated polyisobutene, isohexadecane, mineral oil, ethylhexyl palmitate, dioctyl ether or caprylic/capric triglyceride, or a mixture of dioctyl ether and caprylic/capric triglyceride.
In the present invention, the content of the oil is preferably 6.0 to 8.0%, for example, 7%.
In the present invention, the water generally refers to deionized water.
In the present invention, "the sum of the weight percentages of the components is 100%" is understood to mean that the sum of the weight percentages of the components in the formulation of the fat-containing lyophilized preparation is 100%, and the components are not limited to the main emulsifier, the auxiliary emulsifier, the fat and the water.
In a preferred embodiment, the pre-formulation liquid of the lyophilized preparation comprises the following components in percentage by weight: 12% polyglycerol-6 dicaprate; 6% of polyethylene glycol-8 caprylic/capric glycerides and 7% of hydrogenated polyisobutene.
In a preferred embodiment, the pre-formulation liquid of the lyophilized preparation comprises the following components in percentage by weight: 9% polyglycerol-6 dicaprate, 6% polyethylene glycol-6 caprylic/capric glycerides and 7% isohexadecane.
In a preferred embodiment, the pre-formulation liquid of the lyophilized preparation comprises the following components in percentage by weight: 10% of polyglycerol-6 dicaprate, 6% of polyethylene glycol-8 caprylic/capric glycerides and 7% of mineral oil.
In a preferred embodiment, the pre-formulation liquid of the lyophilized preparation comprises the following components in percentage by weight: 10% polyglycerol-6 dicaprate, 7% polyethylene glycol-6 caprylic/capric glycerides and 7% ethylhexyl palmitate.
In a preferred embodiment, the pre-formulation liquid of the lyophilized preparation comprises the following components in percentage by weight: 9% polyglycerol-6 dicaprate, 8% polyethylene glycol-6 caprylic/capric glycerides, 3.5% dioctyl ether and 3.5% caprylic/capric triglycerides.
In a preferred embodiment, the pre-formulation liquid of the lyophilized preparation comprises the following components in percentage by weight: 7% polyglycerol-6 dicaprate, 7% polyethylene glycol-6 caprylic/capric glycerides and 7% dioctyl ether.
In a preferred embodiment, the pre-formulation liquid of the lyophilized preparation comprises the following components in percentage by weight: 12% polyglycerol-6 dicaprate, 8% polyethylene glycol-6 caprylic/capric glycerides and 7% caprylic/capric triglycerides.
In the above preferred embodiments, it should be understood that the pre-formulation of the lyophilized formulation still satisfies the condition that the sum of the weight percentages of the components is 100%, calculated as weight percentage.
In the present invention, the pre-formulation of lyophilized formulation preferably further comprises an additive.
Wherein the content of the additive is preferably 0 to 85.9%, but not 0, more preferably 0 to 40%, but not 0.
Wherein the additive preferably comprises one or more of a skeletal support, a binder, an anionic surfactant, a skin feel modifier, an active ingredient, a pH adjuster, a chelating agent, a humectant, a permeation enhancer, a fragrance, a blocking agent, a buffering agent, an antioxidant, a light stabilizer, a skin conditioning agent, a cooling agent, and an emollient, and more preferably comprises one or more of a skeletal support, an anionic surfactant, a binder, and an active ingredient.
Wherein the skeleton support agent is preferably one or more of saccharides, sugar alcohols and polysaccharides, more preferably one or more of mannitol, erythritol, trehalose, dendrobium candidum polysaccharide, alpha-mannans and sorbitol, still more preferably erythritol, alpha-mannans, trehalose, mannitol or sorbitol.
Wherein the content of the skeletal support agent is preferably 0.1 to 10%, for example 1%, 5%, 7% or 10%.
Wherein the binder is preferably one or more of polyethylene glycol-120 methyl glucose dioleate, polyethylene glycol-250 distearate, polyethylene glycol-150 distearate, acid bean gum, xanthan gum and cellulose, more preferably one or more of polyethylene glycol-120 methyl glucose dioleate, polyethylene glycol-250 distearate and xanthan gum.
Wherein the binder content is preferably 0 to 3.0%, for example 2.4%, 2.5% or 3%.
Wherein the anionic surfactant is preferably an amino acid surfactant, more preferably one or more of potassium cocoyl glycinate, sodium lauroyl sarcosinate, sodium lauroyl glutamate, disodium cocoyl glutamate and sodium stearoyl glutamate, still more preferably potassium cocoyl glycinate, sodium lauroyl sarcosinate, sodium stearoyl glutamate or disodium cocoyl glutamate.
Wherein the anionic surfactant is preferably present in an amount of 0 to 0.2%, for example 0.075% or 0.9%.
Wherein the skin feel modifier is preferably one or more of polyhydric alcohols such as glycerin, propylene glycol, butylene glycol, and pentylene glycol, and substances having skin feel improving effects such as bis-polyethylene glycol-18 methyl ether dimethylsilane and polyethylene glycol/polypropylene glycol-17/6 copolymer.
Wherein the active ingredient is preferably one or more of nicotinamide, ascorbic acid, ascorbyl glucoside, sodium ascorbyl phosphate, 3-o-ethyl ascorbic acid, caffeine, ascorbyl palmitate, retinol propionate, tocopherol, tocopheryl acetate, vitamin E, citric acid, astaxanthin, resveratrol, glutathione, oligopeptide-1, acetyl hexapeptide-8, a plant extract and yeast/rice fermentation product filtrate, more preferably one or more of nicotinamide, caffeine, tocopherol, astaxanthin or resveratrol.
Wherein the content of the active ingredient is preferably 0 to 10.5%, for example 0.0005%, 0.3%, 1%, 6% or 10.5%.
Wherein the additive preferably does not include a preservative.
In a preferred embodiment, the pre-formulation of the lyophilized formulation comprises the following components in weight percent: 12% polyglycerol-6 dicaprate; 6% of polyethylene glycol-8 caprylic/capric glyceride, 7% of hydrogenated polyisobutene, 5% of erythritol, 0.09% of potassium cocoyl glycinate, 3% of polyethylene glycol-120 methyl glucose dioleate and 6% of nicotinamide, and the balance of water.
In a preferred embodiment, the pre-formulation of the lyophilized formulation comprises the following components in weight percent: 9% of polyglycerol-6 dicaprate, 6% of polyethylene glycol-6 caprylic/capric glycerides, 7% of isohexadecane, 10% of alpha-mannide, 0.09% of sodium lauroyl sarcosinate, 2.4% of polyethylene glycol-250 distearate, 5% of nicotinamide, 5% of caffeine and 0.5% of resveratrol, and the balance of water.
In a preferred embodiment, the pre-formulation of the lyophilized formulation comprises the following components in weight percent: 10% of polyglycerol-6 dicaprate, 6% of polyethylene glycol-8 caprylic/capric glyceride, 7% of mineral oil, 1% of trehalose, 0.09% of sodium stearoyl glutamate and 1% of tocopherol, and the balance of water.
In a preferred embodiment, the pre-formulation of the lyophilized formulation comprises the following components in weight percent: 10% of polyglycerol-6 dicaprate, 7% of polyethylene glycol-6 caprylic/capric glyceride, 7% of ethylhexyl palmitate, 5% of mannitol, 0.09% of potassium cocoyl glycinate, 2.4% of polyethylene glycol-250 distearate and 0.3% of oligopeptide-1, and the balance of water.
In a preferred embodiment, the pre-formulation of the lyophilized formulation comprises the following components in weight percent: 9% of polyglycerol-6 dicaprate, 8% of polyethylene glycol-6 caprylic/capric glyceride, 3.5% of dioctyl ether, 3.5% of caprylic/capric triglyceride, 7% of sorbitol, 0.075% of disodium cocoyl glutamate, 2.4% of polyethylene glycol-250 distearate, 0.1% of xanthan gum and 0.0005% of astaxanthin, and the balance of water.
In a preferred embodiment, the pre-formulation of the lyophilized formulation comprises the following components in weight percent: 7% of polyglycerol-6 dicaprate, 7% of polyethylene glycol-6 caprylic/capric glyceride and 7% of dioctyl ether, and the balance of water.
In a preferred embodiment, the pre-formulation of the lyophilized formulation comprises the following components in weight percent: 12% of polyglycerol-6 dicaprate, 8% of polyethylene glycol-6 caprylic/capric glycerides and 7% of caprylic/capric triglycerides, the balance being water.
The invention also provides a preparation method of the pre-preparation liquid of the freeze-dried preparation containing the grease, which comprises the following steps:
s1, adding the main emulsifier and the grease into an oil phase pot, and heating to 50-60 ℃ to obtain a first raw material;
adding the auxiliary emulsifier and the water into a water phase pot, and heating to 50-60 ℃ to obtain a second raw material;
s2, respectively vacuumizing the first raw material and the second raw material and stirring, or vacuumizing a mixture of the first raw material and the second raw material to obtain a microemulsion;
s3, cooling the microemulsion to below 40 ℃;
when the pre-formulation liquid for lyophilized preparation contains, in addition to the main emulsifier, the auxiliary emulsifier, the fat and the water, a water-soluble component and/or an oil-soluble component such as one or more of a skeleton support, an anionic surfactant, a binder and an oil-soluble active ingredient, the water-soluble component is added to the aqueous phase pot in the step S1; adding the oil soluble component to the oil phase pan;
wherein the water-soluble component does not contain a water-soluble additive that loses bioactivity above 40 ℃, the oil-soluble component does not contain an oil-soluble additive that loses bioactivity above 40 ℃, the water-soluble additive that loses bioactivity above 40 ℃ and the oil-soluble additive that loses bioactivity above 40 ℃ are added after the step S3.
In S2, the stirring is generally continued until the resulting microemulsion is clear and transparent.
In S2, preferably, the second raw material after being vacuumized is added to the first raw material after being vacuumized and then stirred, so that the prepared liquid before the freeze-dried preparation has higher transparency and smaller particle size.
In S3, preferably, the water-soluble additive that loses bioactivity at a temperature higher than 40 ℃ and/or the oil-soluble additive that loses bioactivity at a temperature higher than 40 ℃ are added and cooled to a temperature below 38 ℃.
The invention also provides a freeze-drying protective agent for oil, which comprises the following components in percentage by weight: 6.0 to 12 percent of main emulsifier, 3.0 to 7.0 percent of auxiliary emulsifier and water, wherein the sum of the weight percentages of the components is 100 percent;
wherein the main emulsifier has a hydrophilic-lipophilic balance value of 11 or less; the coemulsifier has a hydrophilic-lipophilic balance of 12.5 or more.
In the present invention, the kind or content of the main emulsifier may be as described above.
In the present invention, the kind or content of the coemulsifier may be as described above.
In the invention, the grease freeze-drying protective agent can comprise grease and additives as described above; the type or amount of the grease may be as described above; the type or amount of the additive may be as described above.
The invention also provides a preparation method of the grease freeze-drying protective agent, which comprises the following steps:
s1, adding the main emulsifier into an oil phase pot, and heating to 50-60 ℃ to obtain a first raw material;
adding the auxiliary emulsifier and the water into a water phase pot, and heating to 50-60 ℃ to obtain a second raw material;
s2, respectively vacuumizing the first raw material and the second raw material and stirring, or vacuumizing a mixture of the first raw material and the second raw material to obtain a semi-finished product of the protective agent;
s3, cooling the semi-finished product of the protective agent to below 40 ℃;
when the oil freeze-drying protecting agent contains one or more of other water-soluble or oil-soluble components such as a skeleton supporting agent, an anionic surfactant, a binder and an oil-soluble active ingredient, the other water-soluble components are added to the aqueous phase pot in the step S1; adding the other oil-soluble components to the oil phase pan; wherein the water-soluble component does not contain a water-soluble additive that loses bioactivity above 40 ℃, the oil-soluble component does not contain an oil-soluble additive that loses bioactivity above 40 ℃, and the water-soluble and oil-soluble additives that lose bioactivity above 40 ℃ are added after step S3.
The invention also provides a freeze-dried preparation, which is prepared from the pre-preparation liquid of the freeze-dried preparation containing the grease.
Preferably, the preparation method of the freeze-dried preparation comprises the following steps:
s1, pre-freezing the pre-preparation liquid of the freeze-dried preparation for 24-48 hours (for example, 48 hours) at-70 to-40 ℃ (for example, at-50 ℃), so as to obtain the pre-preparation liquid of the pre-frozen freeze-dried preparation;
s2, heating the pre-frozen pre-preparation liquid of the freeze-dried preparation to-40-10 ℃ under the vacuum condition of 0.05-0.1MPa (for example, 0.08 MPa), and sublimating for 10-24 hours to obtain the pre-preparation liquid of the freeze-dried preparation after sublimation;
s3, reducing the vacuum degree to 0.005-0.01 Mpa (e.g. 0.008 Mpa) in 0.1-2 min (e.g. 1 min), and performing analytical drying at 0-10 ℃ (e.g. 0 ℃) for 4-12 h (e.g. 6 h) to obtain a freeze-dried composition semi-finished product;
s4, vacuum drying the semi-finished product of the freeze-dried composition at 0-10 ℃ (e.g. 0 ℃) for 4-12 hours (e.g. 6 hours).
In S1, the prefreezing is preferably performed in a lyophilizer.
In S2, the pre-frozen pre-lyophilized preparation solution is heated to-40 to-20 ℃ (e.g., 30 ℃ below zero) under the vacuum condition of 0.05-0.1MPa (e.g., 0.08 MPa), sublimated for 10-24 hours (e.g., 12 hours); continuously heating to-20-0 ℃ within 0.1-2 min (for example, 1 min), sublimating for 10-24 h (for example, 12 h); heating to 0-10deg.C (e.g. 0deg.C) within 0.1-2 min (e.g. 1 min), and vacuum sublimating for 10-24 h (e.g. 12 h) to obtain sublimated lyophilized preparation pre-preparation liquid. The temperature and time of each sublimation can be determined by observing the drying state of the liquid preparation sample before freeze-drying the preparation, and the step S3 can be performed after the drying is completed.
The invention also provides a freeze-dried essence which is prepared from the freeze-dried preparation.
Wherein, the freeze-dried preparation is preferably added into water.
Wherein, preferably, the appearance of the freeze-dried essence is transparent or semitransparent.
Wherein, preferably, the particle size of the freeze-dried essence is less than 500nm.
On the basis of conforming to the common knowledge in the field, the above preferred conditions can be arbitrarily combined to obtain the preferred examples of the invention.
The reagents and materials used in the present invention are commercially available.
The invention has the positive progress effects that:
the preparation method of the pre-preparation liquid of the freeze-dried preparation has the advantages of simple process, low production cost, transparent or semitransparent appearance, good stability and no demulsification, layering and other problems. The freeze-dried preparation is prepared by freeze-drying the pre-preparation liquid of the freeze-dried preparation, when the freeze-dried preparation is used, the freeze-dried preparation is dissolved in water to form freeze-dried essence, and the problems of demulsification, layering, difficult dissolution and the like of the essence cannot occur, so that the stability is good, and the shelf life is long; the essence solution keeps semitransparent or transparent appearance, is convenient for consumers to use, and can provide moisture, softness and luster for skin, reduce the percutaneous water loss rate of the skin and improve the absorption of functional components of cosmetics.
In a preferred embodiment of the present invention, a lyophilized formulation can be prepared without the need for a matrix support and a binder. Can avoid the addition of any preservative and reduce the damage to the microemulsion system. The lyophilized preparation can be added with fat-soluble functional components and heat-sensitive active components, and can avoid risk problems during storage and logistics transportation.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
Example 1
The following components are weighed according to the formula according to the weight percentage: 12.0% of polyglycerol-6 dicaprate, 6.0% of polyethylene glycol-8 caprylic/capric glyceride, 7.0% of hydrogenated polyisobutene, 5.0% of erythritol, 0.09% of sodium cocoyl glycinate, 3% of polyethylene glycol-120 methyl glucose dioleate, 6% of nicotinamide and the balance of deionized water.
Adding polyglycerol-6 dicaprate and hydrogenated polyisobutene into an oil phase pot, and heating to 50-60 ℃; adding polyethylene glycol-8 caprylic/capric glyceride, erythritol, sodium cocoyl glycinate, polyethylene glycol-120 methyl glucose dioleate and water into a water phase pot, and heating to 50-60 ℃; pumping the oil phase pot raw material and the water phase pot raw material into an emulsifying pot in vacuum, stirring uniformly until the materials are clear and transparent, cooling the microemulsion to below 40 ℃, adding nicotinamide, continuously cooling to 38 ℃, and discharging to obtain the pre-freeze-drying liquid.
Taking 2g of pre-freeze preparation liquid, quick-freezing to-50 ℃, and then placing the pre-freeze preparation liquid into a freeze dryer for pre-freezing for 48 hours. Heating to-30deg.C for vacuum sublimation for 12 hr under vacuum condition of 0.08MPa for 1min after pre-freezing; after 12h, continuously heating the temperature to-10 ℃ within 1min, and sublimating for 12h in vacuum; finally, the temperature is raised to 0 ℃ in 1min for vacuum sublimation for 12h. And (3) reducing the vacuum degree to 0.008MPa within 1min after vacuum sublimation of the pre-frozen liquid, and performing resolution drying for 6h at the temperature of 0 ℃ to obtain a semi-finished product of the freeze-dried composition. And (5) continuously vacuum drying the semi-finished product of the freeze-dried composition at the temperature of 0 ℃ for 6 hours to obtain a freeze-dried preparation.
When in use, 3g of deionized water is used for diluting the prepared freeze-dried preparation, and the semitransparent or transparent freeze-dried essence can be obtained. The freeze-dried essence has good stability after being placed for 7 days at room temperature, and the particle size of the product and the particle size after 7 days are not obviously changed.
Example 2
The following components are weighed according to the formula according to the weight percentage: 9.0% of polyglycerol-6 dicaprate, 6.0% of polyethylene glycol-6 caprylic/capric glyceride, 7.0% of isohexadecane, 10.0% of alpha-mannite, 0.09% of sodium lauroyl sarcosinate, 2.4% of polyethylene glycol-250 distearate, 5% of nicotinamide, 5% of caffeine, 0.5% of resveratrol and the balance of deionized water.
Adding polyglycerol-6 dicaprate and isohexadecane into an oil phase pot, and heating to 50-60 ℃; adding polyethylene glycol-6 caprylic/capric glyceride, alpha-manna, sodium lauroyl sarcosinate, polyethylene glycol-250 distearate, caffeine, resveratrol and water into a water phase pot, and heating to 50-60 ℃; pumping the oil phase pot raw material and the water phase pot raw material into an emulsifying pot in vacuum, stirring uniformly until the materials are clear and transparent, cooling the microemulsion to below 40 ℃, adding nicotinamide, continuously cooling to 38 ℃, and discharging to obtain the pre-freeze-drying liquid.
The freeze-dried preparation was prepared in the same manner as in example 1.
When in use, 6g of deionized water is used for diluting the prepared freeze-dried preparation, and the semitransparent or transparent freeze-dried essence can be obtained. The freeze-dried essence has good stability after being placed for 30 days at room temperature, and the particle size of the product and the particle size after 30 days are not obviously changed.
Example 3
The following components are weighed according to the formula according to the weight percentage: 10.0% of polyglycerol-6 dicaprate, 6.0% of polyethylene glycol-8 caprylic/capric glyceride, 7.0% of mineral oil, 1.0% of trehalose, 0.09% of sodium stearyl glutamate, 1% of tocopherol and the balance of deionized water.
Adding polyglycerol-6 dicaprate, mineral oil and tocopherol into an oil phase pot, and heating to 50-60 ℃; adding polyethylene glycol-8 caprylic/capric glyceride, trehalose, sodium stearyl glutamate and water into a water phase pot, and heating to 50-60 ℃; and (3) pumping the oil phase pot raw material and the water phase pot raw material into an emulsifying pot in vacuum, uniformly stirring until the materials are clear and transparent, cooling the microemulsion to below 38 ℃, and discharging to obtain the pre-freeze-drying liquid.
The freeze-dried preparation was prepared in the same manner as in example 1.
When in use, 6g of deionized water is used for diluting the prepared freeze-dried preparation, and the semitransparent or transparent freeze-dried essence can be obtained. The freeze-dried essence has good stability after being placed for 7 days at room temperature, and the particle size of the product and the particle size after 7 days are not obviously changed.
Example 4
The following components are weighed according to the formula according to the weight percentage: 10.0% of polyglycerol-6 dicaprate, 7.0% of polyethylene glycol-6 caprylic/capric glyceride, 7.0% of ethylhexyl palmitate, 5.0% of mannitol, 0.09% of potassium cocoyl glycinate, 2.4% of polyethylene glycol-250 distearate, 0.3% of oligopeptide-1 and the balance of deionized water.
Adding polyglycerol-6 dicaprate and ethylhexyl palmitate into an oil phase pot, and heating to 50-60 ℃; adding polyethylene glycol-6 caprylic/capric glyceride, mannitol, potassium cocoyl glycinate, polyethylene glycol-250 distearate and water into a water phase pot, and heating to 50-60 ℃; pumping the oil phase pot raw material and the water phase pot raw material into an emulsifying pot in vacuum, stirring uniformly until the materials are clear and transparent, cooling the microemulsion to below 40 ℃, adding oligopeptide-1, continuously cooling to 38 ℃, and discharging to obtain the pre-freeze-drying liquid.
The freeze-dried preparation was prepared in the same manner as in example 1.
When in use, 6g of deionized water is used for diluting the prepared freeze-dried preparation, and the semitransparent or transparent freeze-dried essence can be obtained. The freeze-dried essence has good stability after being placed for 30 days at room temperature, and the particle size of the product and the particle size after 30 days are not obviously changed.
Example 5
The following components are weighed according to the formula according to the weight percentage: 9.0% of polyglycerol-6 dicaprate, 8.0% of polyethylene glycol-6 caprylic/capric glyceride, 3.5% of dioctyl ether, 3.5% of caprylic/capric triglyceride, 7% of sorbitol, 0.075% of cocoyl disodium glutamate, 0.1% of xanthan gum, 0.0005% of astaxanthin and the balance of deionized water.
Adding polyglycerol-6 dicaprate, dioctyl ether, caprylic/capric triglyceride into an oil phase pot, and heating to 50-60 ℃; adding polyethylene glycol-6 caprylic/capric glyceride, sorbitol, disodium cocoyl glutamate, xanthan gum and water into a water phase pot, and heating to 50-60 ℃; pumping the oil phase pot raw material and the water phase pot raw material into an emulsifying pot in vacuum, stirring uniformly until the materials are clear and transparent, cooling the microemulsion to below 40 ℃, adding astaxanthin, continuously cooling to 38 ℃, and discharging to obtain the pre-freeze-drying liquid.
The freeze-dried preparation was prepared in the same manner as in example 1.
When in use, 6g of deionized water is used for diluting the prepared freeze-dried preparation, and the semitransparent or transparent freeze-dried essence can be obtained. The freeze-dried essence has good stability after being placed for 7 days at room temperature, and the particle size of the product and the particle size after 7 days are not obviously changed.
Example 6
The following components are weighed according to the formula according to the weight percentage: 7% of polyglycerol-6 dicaprate, 7% of polyethylene glycol-6 caprylic/capric glyceride, 7% of dioctyl ether and the balance of deionized water.
Adding polyglycerol-6 dicaprate and dioctyl ether into an oil phase pot, and heating to 50-60 ℃; adding polyethylene glycol-6 caprylic/capric glyceride and water into a water phase pot, and heating to 50-60 ℃; and (3) pumping the oil phase pot raw material and the water phase pot raw material into an emulsifying pot in vacuum, uniformly stirring until the materials are clear and transparent, cooling the microemulsion to below 40 ℃ and discharging to obtain the pre-freeze-drying liquid.
The freeze-dried preparation was prepared in the same manner as in example 1. The freeze-dried preparation with powdery appearance can not be formed without adding a skeleton supporting agent.
When in use, 6g of deionized water is used for diluting the prepared freeze-dried preparation, and the semitransparent or transparent freeze-dried essence can be obtained. The freeze-dried essence has good stability after being placed for 7 days at room temperature, the particle size of the product and the particle size after 7 days are not obviously changed, and the stability of the freeze-dried essence is not affected without adding a framework supporting agent.
Example 7
The following components are weighed according to the formula according to the weight percentage: 12% of polyglycerol-6 dicaprate, 8% of polyethylene glycol-6 caprylic/capric glyceride, 7% of caprylic/capric triglyceride and the balance of deionized water.
Adding polyglycerol-6 dicaprate and caprylic/capric triglyceride into an oil phase pot, and heating to 50-60 ℃; adding polyethylene glycol-6 caprylic/capric glyceride and water into a water phase pot, and heating to 50-60 ℃; and (3) pumping the oil phase pot raw material and the water phase pot raw material into an emulsifying pot in vacuum, uniformly stirring until the materials are clear and transparent, cooling the microemulsion to below 40 ℃ and discharging to obtain the pre-freeze-drying liquid.
The freeze-dried preparation was prepared in the same manner as in example 1. The freeze-dried preparation with powdery appearance can not be formed without adding a skeleton supporting agent.
When in use, 6g of deionized water is used for diluting the prepared freeze-dried preparation, and the semitransparent or transparent freeze-dried essence can be obtained. The freeze-dried essence has good stability after being placed for 7 days at room temperature, the particle size of the product and the particle size after 7 days are not obviously changed, and the stability of the freeze-dried essence is not affected without adding a framework supporting agent.
The components and contents of examples 1 to 7, and the properties of the products are shown in Table 1.
TABLE 1 Components, content (mass%) and product Properties of examples 1 to 7
Comparative example 1
The components and amounts of comparative example 1 are as follows: 2% of polyethylene glycol-20 methyl glucose sesquistearate (HLB value is 15), 0.6% of acrylic acid (esters) and C10-30 alkanol acrylate cross-linked polymer, 6% of caprylic acid/capric acid triglyceride and the balance of deionized water. The preparation method of comparative example 1 was the same as in examples 1 to 7.
The freeze-dried preparation prepared after freeze-drying is not easy to dissolve in water, the appearance of the freeze-dried essence is an aqueous solution with white particles floating, and the freeze-dried essence is still in a layered state after being placed at room temperature for 7 days; after rehydration, the phenomenon of partial insolubility still exists, and delamination is caused after long-term standing.
Comparative example 2
The components and amounts of comparative example 2 are as follows: 2% of polyethylene glycol-40 hydrogenated castor oil PCA isostearate (HLB value is 11), 2% of polyethylene glycol-40 hydrogenated castor oil (HLB value is 12.5), 6% of caprylic/capric triglyceride, 0.2% of acrylic acid (esters) and C10-30 alkanol acrylate crosslinked polymer are additionally added, and the balance of deionized water. The preparation method was the same as in examples 1 to 7.
The freeze-dried preparation prepared after freeze-drying is not easy to dissolve in water, the appearance of the freeze-dried essence is turbid liquid with insoluble particles, and the freeze-dried preparation is still in a layered state after being placed at room temperature for 7 days.
Claims (19)
1. The pre-preparation liquid of the freeze-dried preparation containing the grease is characterized in that the pre-preparation liquid comprises any one of the following components (1) - (3) in percentage by weight:
(1) The formula comprises the following components in percentage by weight: 6.0-12% of main emulsifier, 3.0-7.0% of auxiliary emulsifier, 5.0-9.0% of grease and water, wherein the sum of the weight percentages of the components is 100%;
wherein the main emulsifier has a hydrophilic-lipophilic balance value of 11 or less; the hydrophilic-lipophilic balance value of the auxiliary emulsifier is more than 12.5;
the main emulsifier is polyglycerol-6 dicaprate;
the auxiliary emulsifier is one or more of polyethylene glycol-6 caprylic acid/capric acid glyceride, polyethylene glycol-7 caprylic acid/capric acid glyceride and polyethylene glycol-8 caprylic acid/capric acid glyceride;
the grease is one or more of alkanes, ethers, esters and triglycerides;
the alkane is one or more of mineral oil, isohexadecane and hydrogenated polyisobutene;
the ether is dioctyl ether;
the esters are one or more of dioctyl carbonate, isopropyl myristate, isopropyl palmitate and ethylhexyl palmitate;
the triglycerides are one or more of triglyceride of tri (ethylhexanoate) and caprylic/capric triglyceride;
(2) The composite material comprises the following components in percentage by weight: 9% of polyglycerol-6 dicaprate, 8% of polyethylene glycol-6 caprylic/capric glyceride, 3.5% of dioctyl ether, 3.5% of caprylic/capric triglyceride and water, wherein the sum of the weight percentages of the components is 100%;
(3) The composite material comprises the following components in percentage by weight: 12% of polyglycerol-6 dicaprate, 8% of polyethylene glycol-6 caprylic/capric glyceride, 7% of caprylic/capric triglyceride and water, wherein the sum of the weight percentages of the components is 100%.
2. The pre-formulation for a lyophilized formulation comprising an oil and fat according to claim 1, wherein the main emulsifier has a hydrophilic-lipophilic balance of 9 to 11;
and/or, the primary emulsifier is a nonionic emulsifier;
and/or the content of the main emulsifier is 7.0-10.0%;
and/or the hydrophilic-lipophilic balance value of the auxiliary emulsifier is 12.5-14;
and/or, the co-emulsifier is a nonionic emulsifier;
and/or the content of the auxiliary emulsifier is 5.0-7.0%;
and/or the content of the grease is 6.0-8.0%.
3. The fat-containing lyophilized preparation pre-formulation according to claim 2, wherein the main emulsifier is contained in an amount of 7%, 9% or 10%;
and/or the content of the auxiliary emulsifier is 6% or 7%;
and/or the content of the grease is 7%;
and/or the grease is hydrogenated polyisobutene, isohexadecane, mineral oil, ethylhexyl palmitate, dioctyl ether or caprylic/capric triglyceride, or a mixture of dioctyl ether and caprylic/capric triglyceride.
4. A pre-formulation for a lyophilized formulation comprising oil as defined in any one of claims 1 to 3, wherein the pre-formulation for a lyophilized formulation in formula (1) comprises the following components in weight percent: 12% polyglycerol-6 dicaprate; 6% of polyethylene glycol-8 caprylic/capric glycerides and 7% of hydrogenated polyisobutene;
or, the pre-freeze-dried preparation liquid in the formula (1) comprises the following components in percentage by weight: 9% polyglycerol-6 dicaprate, 6% polyethylene glycol-6 caprylic/capric glycerides and 7% isohexadecane;
or, the pre-freeze-dried preparation liquid in the formula (1) comprises the following components in percentage by weight: 10% of polyglycerol-6 dicaprate, 6% of polyethylene glycol-8 caprylic/capric glycerides and 7% of mineral oil;
or, the pre-freeze-dried preparation liquid in the formula (1) comprises the following components in percentage by weight: 10% polyglycerol-6 dicaprate, 7% polyethylene glycol-6 caprylic/capric glycerides and 7% ethylhexyl palmitate;
or, the pre-freeze-dried preparation liquid in the formula (1) comprises the following components in percentage by weight: 7% polyglycerol-6 dicaprate, 7% polyethylene glycol-6 caprylic/capric glycerides and 7% dioctyl ether.
5. A pre-formulation for a lyophilized formulation comprising an oil as defined in any one of claims 1 to 3, wherein the pre-formulation for a lyophilized formulation has a transparent or translucent appearance;
and/or the particle size of the pre-formulation of the lyophilized formulation is less than 500nm;
and/or, the pre-formulation of the lyophilized formulation further comprises an additive;
wherein the additive comprises one or more of a skeletal support, a binder, an anionic surfactant, a skin feel modifier, an active ingredient, a pH adjuster, a chelating agent, a humectant, a permeation enhancer, a fragrance, a blocking agent, a buffer, an antioxidant, a light stabilizer, a skin conditioning agent, a cooling agent, and an emollient.
6. The lipid-containing lyophilized preparation pre-formulation of claim 5, wherein the particle size of the lyophilized preparation pre-formulation is less than 250nm;
and/or the content of the additive is 0-85.9%, but not 0;
and/or the additive comprises one or more of a skeletal support, an anionic surfactant, a binder, and an active ingredient;
and/or the additive does not include a preservative.
7. The pre-formulation for a lyophilized preparation containing oil according to claim 6, wherein the content of the additive is 0 to 40% but not 0.
8. The lipid-containing lyophilized preparation pre-formulation according to claim 5, wherein the skeleton support agent is a saccharide and/or a sugar alcohol;
and/or the content of the skeleton supporting agent is 0.1-10%;
and/or the binder is one or more of polyethylene glycol-120 methyl glucose dioleate, polyethylene glycol-250 distearate, polyethylene glycol-150 distearate, acid bean gum, xanthan gum and cellulose;
and/or the content of the binder is 0-3.0%;
and/or, the anionic surfactant is an amino acid surfactant;
and/or the content of the anionic surfactant is 0-0.2%;
and/or the skin feel modifier is one or more of glycerin, propylene glycol, butylene glycol, pentylene glycol, bis-polyethylene glycol-18 methyl ether dimethylsilane and polyethylene glycol/polypropylene glycol-17/6 copolymer;
and/or the active ingredient is one or more of nicotinamide, ascorbic acid, ascorbyl glucoside, sodium ascorbyl phosphate, 3-o-ethyl ascorbic acid, caffeine, ascorbyl palmitate, retinol propionate, tocopherol, tocopheryl acetate, vitamin E, citric acid, astaxanthin, resveratrol, glutathione, oligopeptide-1, acetyl hexapeptide-8, a plant extract and yeast/rice fermentation product filtrate;
and/or the content of the active ingredient is 0-10.5%.
9. The lipid-containing lyophilized preparation pre-formulation of claim 8, wherein the backbone support agent is one or more of mannitol, erythritol, trehalose, dendrobium candidum polysaccharide, alpha-mannans, and sorbitol;
and/or the binder is one or more of polyethylene glycol-120 methyl glucose dioleate, polyethylene glycol-250 distearate and xanthan gum;
and/or the anionic surfactant is one or more of potassium cocoyl glycinate, sodium lauroyl sarcosinate, sodium lauroyl glutamate, disodium cocoyl glutamate and sodium stearoyl glutamate;
and/or the active ingredient is one or more of nicotinamide, caffeine, tocopherol, astaxanthin or resveratrol.
10. The lipid-containing lyophilized preparation pre-formulation of claim 9, wherein the matrix support agent is erythritol, a-mannans, trehalose, mannitol, or sorbitol;
and/or the anionic surfactant is potassium cocoyl glycinate, sodium lauroyl sarcosinate, sodium stearyl glutamate or disodium cocoyl glutamate.
11. The lipid-containing lyophilized preparation pre-formulation of claim 8, wherein the matrix support agent is a polysaccharide.
12. The freeze-drying protective agent for the grease is characterized by comprising any one of the following components (1) - (3) in percentage by weight:
(1) The formula comprises the following components in percentage by weight: 6.0-12% of main emulsifier, 3.0-7.0% of auxiliary emulsifier and water, wherein the sum of the weight percentages of the components is 100%;
wherein the main emulsifier has a hydrophilic-lipophilic balance value of 11 or less; the hydrophilic-lipophilic balance value of the auxiliary emulsifier is more than 12.5;
the main emulsifier is polyglycerol-6 dicaprate;
the auxiliary emulsifier is one or more of polyethylene glycol-6 caprylic acid/capric acid glyceride, polyethylene glycol-7 caprylic acid/capric acid glyceride and polyethylene glycol-8 caprylic acid/capric acid glyceride;
the grease is one or more of alkanes, ethers, esters and triglycerides;
the alkane is one or more of mineral oil, isohexadecane and hydrogenated polyisobutene;
the ether is dioctyl ether;
the esters are one or more of dioctyl carbonate, isopropyl myristate, isopropyl palmitate and ethylhexyl palmitate;
the triglycerides are one or more of triglyceride of tri (ethylhexanoate) and caprylic/capric triglyceride;
(2) The formula comprises the following components in percentage by weight: 9% of polyglycerol-6 dicaprate, 8% of polyethylene glycol-6 caprylic/capric glyceride, 3.5% of dioctyl ether, 3.5% of caprylic/capric triglyceride and water, wherein the sum of the weight percentages of the components is 100%;
(3) The formula comprises the following components in percentage by weight: 12% of polyglycerol-6 dicaprate, 8% of polyethylene glycol-6 caprylic/capric glyceride, 7% of caprylic/capric triglyceride and water, wherein the sum of the weight percentages of the components is 100%.
13. A method for preparing the fat-containing lyophilized preparation precursor solution according to any one of claims 1 to 11, comprising the steps of:
s1, adding the main emulsifier and the grease into an oil phase pot, and heating to 50-60 ℃ to obtain a first raw material;
adding the auxiliary emulsifier and the water into a water phase pot, and heating to 50-60 ℃ to obtain a second raw material;
s2, respectively vacuumizing the first raw material and the second raw material and stirring, or vacuumizing a mixture of the first raw material and the second raw material to obtain a microemulsion;
s3, cooling the microemulsion to below 40 ℃.
14. The method for preparing a pre-formulation for a lyophilized formulation containing a fat as claimed in claim 13, wherein for water-soluble components and/or oil-soluble components other than the main emulsifier, the auxiliary emulsifier, the fat and the water, the water-soluble components are added to the aqueous phase pot in the step S1; adding the oil soluble component to the oil phase pan;
the water-soluble components and/or oil-soluble components other than the main emulsifier, the co-emulsifier, the grease, and the water include one or more of a backbone support, an anionic surfactant, a binder, and an oil-soluble active ingredient;
wherein in step S1, the water-soluble component does not contain a water-soluble additive which loses bioactivity above 40 ℃, the oil-soluble component does not contain an oil-soluble additive which loses bioactivity above 40 ℃, and the water-soluble additive which loses bioactivity above 40 ℃ and/or the oil-soluble additive which loses bioactivity above 40 ℃ are added after step S3.
15. The method for preparing a pre-formulation for a lyophilized preparation containing oil and fat according to claim 14, wherein in S3, the water-soluble additive which loses bioactivity at a temperature higher than 40 ℃ and/or the oil-soluble additive which loses bioactivity at a temperature higher than 40 ℃ are added and cooled to a temperature lower than 38 ℃.
16. A lyophilized preparation characterized by being prepared from the lipid-containing pre-lyophilized preparation formulation according to any one of claims 1 to 11;
the preparation method of the freeze-dried preparation comprises the following steps:
s1, pre-freezing the pre-preparation liquid of the freeze-dried preparation at the temperature of-70 to-40 ℃ for 24-48 hours to obtain the pre-preparation liquid of the pre-frozen freeze-dried preparation;
s2, heating the pre-frozen pre-preparation liquid of the freeze-dried preparation to-40-10 ℃ under the vacuum condition of 0.05-0.1MPa, and sublimating for 10-24 hours to obtain the pre-preparation liquid of the sublimated freeze-dried preparation;
s3, reducing the vacuum degree of the sublimated pre-preparation liquid of the freeze-dried preparation to 0.005-0.01 mpa within 0.1-2 min, and performing analytical drying at 0-10 ℃ for 4-12 h to obtain a semi-finished product of the freeze-dried composition;
s4, drying the semi-finished product of the freeze-dried composition in vacuum at the temperature of 0-10 ℃ for 4-12 hours.
17. The lyophilized preparation according to claim 16, wherein in S2, the pre-frozen preparation liquid is heated to-40 to-20 ℃ under a vacuum condition of 0.05-0.1MPa, and sublimated for 10-24 hours; continuously heating to-20-0 ℃ within 0.1-2 min, and sublimating for 10-24 h; heating to 0-10 ℃ within 0.1-2 min, and sublimating for 10-24 h in vacuum to obtain the sublimated pre-preparation liquid of the freeze-dried preparation.
18. A lyophilized concentrate, characterized in that it is prepared from a lyophilized formulation as defined in claim 16 or 17;
the preparation method of the freeze-dried essence comprises the following steps: adding the freeze-dried preparation into water.
19. The lyophilized concentrate of claim 18, wherein the lyophilized concentrate is transparent or translucent in appearance;
and/or, the particle size of the freeze-dried essence is less than 500nm.
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| CN101428002A (en) * | 2008-11-20 | 2009-05-13 | 沈阳万爱普利德医药科技有限公司 | Paclitaxel freeze drying microemulsion for injection and method of producing the same |
| CN102389403A (en) * | 2009-09-01 | 2012-03-28 | 广州市隆赋药业有限公司 | Freeze dried monophosphate adenine arabinoside powder injection for injection and preparation method thereof |
| WO2018028531A1 (en) * | 2016-08-11 | 2018-02-15 | 董玲 | Lyophilized preparation and preparation method therefor |
| CN108670941A (en) * | 2018-06-15 | 2018-10-19 | 四川驰鼎盛通生物科技有限公司 | A kind of preparation method of essence and its essence and compound stem cell factor freeze-dried powder |
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| US6761903B2 (en) * | 1999-06-30 | 2004-07-13 | Lipocine, Inc. | Clear oil-containing pharmaceutical compositions containing a therapeutic agent |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101428002A (en) * | 2008-11-20 | 2009-05-13 | 沈阳万爱普利德医药科技有限公司 | Paclitaxel freeze drying microemulsion for injection and method of producing the same |
| CN102389403A (en) * | 2009-09-01 | 2012-03-28 | 广州市隆赋药业有限公司 | Freeze dried monophosphate adenine arabinoside powder injection for injection and preparation method thereof |
| WO2018028531A1 (en) * | 2016-08-11 | 2018-02-15 | 董玲 | Lyophilized preparation and preparation method therefor |
| CN108670941A (en) * | 2018-06-15 | 2018-10-19 | 四川驰鼎盛通生物科技有限公司 | A kind of preparation method of essence and its essence and compound stem cell factor freeze-dried powder |
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Address after: 201403 Shanghai City, Fengxian District Lifenglu No. 12 Patentee after: Shanghai Natural Hall Group Co.,Ltd. Country or region after: China Address before: 201403 Shanghai City, Fengxian District Lifenglu No. 12 Patentee before: JALA Group Co. Country or region before: China |