CN101869302B - Micro-emulsion calcium preparation and preparation method as well as application thereof - Google Patents
Micro-emulsion calcium preparation and preparation method as well as application thereof Download PDFInfo
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- CN101869302B CN101869302B CN2009100826720A CN200910082672A CN101869302B CN 101869302 B CN101869302 B CN 101869302B CN 2009100826720 A CN2009100826720 A CN 2009100826720A CN 200910082672 A CN200910082672 A CN 200910082672A CN 101869302 B CN101869302 B CN 101869302B
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- 239000011575 calcium Substances 0.000 title claims abstract description 66
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title claims abstract description 63
- 229910052791 calcium Inorganic materials 0.000 title claims abstract description 63
- 239000004530 micro-emulsion Substances 0.000 title claims abstract description 63
- 238000002360 preparation method Methods 0.000 title claims abstract description 51
- 229940088594 vitamin Drugs 0.000 claims abstract description 28
- 229930003231 vitamin Natural products 0.000 claims abstract description 28
- 235000013343 vitamin Nutrition 0.000 claims abstract description 28
- 239000011782 vitamin Substances 0.000 claims abstract description 28
- 150000003722 vitamin derivatives Chemical class 0.000 claims abstract description 26
- 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 abstract description 25
- 239000000600 sorbitol Substances 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000004064 cosurfactant Substances 0.000 claims abstract description 16
- 239000012071 phase Substances 0.000 claims abstract description 15
- 239000004094 surface-active agent Substances 0.000 claims abstract description 13
- 239000007788 liquid Substances 0.000 claims abstract description 7
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 6
- 235000010445 lecithin Nutrition 0.000 claims abstract description 6
- 229940067606 lecithin Drugs 0.000 claims abstract description 6
- 239000000787 lecithin Substances 0.000 claims abstract description 6
- 229960005069 calcium Drugs 0.000 claims description 55
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 44
- 238000003756 stirring Methods 0.000 claims description 30
- 239000008347 soybean phospholipid Substances 0.000 claims description 21
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 20
- 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 17
- 239000004227 calcium gluconate Substances 0.000 claims description 16
- 229960004494 calcium gluconate Drugs 0.000 claims description 16
- 235000013927 calcium gluconate Nutrition 0.000 claims description 16
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical group [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 14
- 239000012153 distilled water Substances 0.000 claims description 13
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 13
- 229920000053 polysorbate 80 Polymers 0.000 claims description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- 238000005303 weighing Methods 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 229920000136 polysorbate Polymers 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 229930003316 Vitamin D Natural products 0.000 claims description 6
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 6
- 239000011710 vitamin D Substances 0.000 claims description 6
- 235000019166 vitamin D Nutrition 0.000 claims description 6
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 6
- 229940046008 vitamin d Drugs 0.000 claims description 6
- 239000012467 final product Substances 0.000 claims description 4
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 239000011719 vitamin A Substances 0.000 claims description 3
- 235000019155 vitamin A Nutrition 0.000 claims description 3
- 229940045997 vitamin a Drugs 0.000 claims description 3
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical class CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 2
- 206010006956 Calcium deficiency Diseases 0.000 claims description 2
- 235000010469 Glycine max Nutrition 0.000 claims description 2
- 244000068988 Glycine max Species 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- -1 polyoxyethylene Polymers 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 12
- 238000010521 absorption reaction Methods 0.000 abstract description 11
- 210000004369 blood Anatomy 0.000 abstract description 5
- 239000008280 blood Substances 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract description 2
- 230000001737 promoting effect Effects 0.000 abstract 2
- 239000000796 flavoring agent Substances 0.000 abstract 1
- 235000013355 food flavoring agent Nutrition 0.000 abstract 1
- 238000009472 formulation Methods 0.000 description 8
- 239000002245 particle Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 3
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 239000000174 gluconic acid Substances 0.000 description 3
- 235000012208 gluconic acid Nutrition 0.000 description 3
- 238000001033 granulometry Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- 239000001639 calcium acetate Substances 0.000 description 1
- 235000011092 calcium acetate Nutrition 0.000 description 1
- 229960005147 calcium acetate Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000007908 nanoemulsion Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 230000005186 women's health Effects 0.000 description 1
Abstract
The invention discloses a micro-emulsion calcium preparation and a preparation method as well as application thereof. In the micro-emulsion calcium preparation, a micro-emulsion structure is used as a carrier of a calcium source, wherein the micro-emulsion structure is a homogeneous system which is composed of an oil phase, a water phase, surfactants and cosurfactants. In the invention, vitamin components are used as the oil phase of the micro-emulsion, lecithin and other components with the functions of reducing blood fat and the like are used as the surfactants of the micro-emulsion, and sorbitol and other components with the function of a flavoring agent are used as the cosurfactants of the micro-emulsion, so that on one hand, the calcium preparation and the vitamin components for promoting calcium absorption can be encapsulated in the same system, and vitamins exist in a liquid form, thereby furthest performing the function of the vitamins for promoting calcium absorption, and on the other hand, various components for forming the micro-emulsion structure are also used as the components for performing curative effect or functions of flavoring and the like, thereby reducing the usage amounts of auxiliary materials. The micro-emulsion calcium preparation of the invention has the advantages of stable system properties, beautiful and transparent appearance, high utilization degree of oral absorption, simple preparation process and the like.
Description
Technical field
The present invention relates to a kind of calcium-supplementing preparation, relate in particular to a kind of micro-emulsion calcium and its preparation method and application, belong to the calcium-supplementing preparation field.
Background technology
Calcareous is very important nutrient in human body, to consist of the topmost element of skeleton, be even more important for the skeleton of developmental child and teenager, growth and the consolidation of tooth, simultaneously also particularly important to the men and women at any age, especially women's health.Can run off every day 600 milligrams calcareous of human body, and the calcium major function is to keep the normal operation of nervous system, muscle, heart, also influential for blood coagulation, controlling of blood pressure aspect.So guarantee to absorb enough calcareous extremely important.
The activity form of vitamin D can bring out a kind of protein that can be combined with calcium at small intestinal, this albumen mass-energy and calcium binding, as a kind of carrier with calcium transport in blood, simultaneously, this protein can also increase mucous membrane of small intestine to the permeability of calcium, and calcium is initiatively entered blood by the mucosa transhipment.The activity form of vitamin D can also directly be had an effect to kidney, promotes that kidney heavily absorbs calcium and phosphorus, thereby reduces losing of calcium and phosphorus.So, must note simultaneously vitamin D when replenishing the calcium, to promote absorption and the utilization of calcium.
Only take calcium (mostly being ionic calcium) preparation as main component, the oral absorption availability is very low for traditional calcium preparation.Present calsium supplement has adding vitamin A or vitamin D, the nutritional labelings such as the adding lecithin that has.But mostly be and simply be mixed and made into tablet or suspendible is made soft capsule.Degree of absorbing is difficult to guarantee.Vitamin and lecithin be difficult to especially play a role (under the two room temperature for grease) in the solid preparation.
The microemulsion structure is found in nineteen forty-three first by Englishize scholar Sculman and Hoar.And formally name in nineteen fifty-nine and to be microemulsion (microemulsion).. the microemulsion structure is the homogeneous system of thermodynamically stable oil-water-surfactant-cosurfactant, and appearance transparent or approximate transparent also equally is divided into W/O and O/W type with general Emulsion, and particle diameter is little, usually between 10-100nm, so also be referred to as nano-emulsion.
Enter after the nineties, microemulsion causes people's attention gradually as the application of pharmaceutical carrier.Microemulsion has great application potential as a kind of new drug carrier.Mainly have following advantage:
(1) microemulsion formulation can improve the dissolubility of insoluble drug, greatly reduces the dose of this type of medicine.
(2) the microemulsion formulation particle diameter is little, can pass through effectively and rapidly gastrointestinal tract epithelial cell, greatly improves the bioavailability of medicine.
(3) microemulsion formulation can be made multiple dosage form, comprises oral formulations, ejection preparation and transdermal absorption formulation.
(4) it is write out a prescription once determining that preparation method is simple.
Summary of the invention
Technical problem to be solved by this invention is to overcome calcium preparation in the existing calcium-supplementing preparation (water) and vitamin (oil) can not be total to technical problem molten so that bioavailability is low, a kind of microemulsion calcium-supplementing preparation is provided, this microemulsion calcium-supplementing preparation utilizes the microemulsion structure that calcium preparation and vitamin ingredients bag are loaded among the individual system, this calcium-supplementing preparation particle diameter is between 10-100nm, has the system stable in properties, appearance looks elegant is transparent, oral absorption availability advantages of higher.
Technical problem to be solved by this invention is achieved through the following technical solutions:
A kind of microemulsion calcium-supplementing preparation, with the carrier of microemulsion structure as the calcium source, the homogeneous system that described microemulsion structure is comprised of oil phase, water, surfactant and cosurfactant;
Wherein, described oil phase is selected from vitamin A, vitamin D or vitamin AD as oil phase;
Described surfactant is one or more mixture that form in soybean phospholipid, lecithin, polyoxyethylene hydrogenated Oleum Ricini, tween 80 or span preferably; More preferably formed by tween 80 and soybean phospholipid;
Described cosurfactant is one or more mixture that form in sorbitol, ethanol, glycerol or glycerol preferably; More preferably formed by sorbitol and ethanol;
Described calcium source is preferably organic calcium, more preferably the organic calcium sources such as calcium carbonate, calcium gluconate, calcium lactate, tricalcium phosphate or calcium acetate;
In order to reach better technique effect, the weight portion of each component is preferably:
Calcium source 10-50 weight portion, oil phase 1-10 weight portion, surfactant 5.5-22 weight portion, cosurfactant 1.5-12 weight portion; Described surfactant preferably is comprised of two kinds of tween 80 and soybean phospholipids independent of one another, that separately use, and wherein, the weight proportion of tween 80 and soybean phospholipid is preferably 5-20: 0.5-2; Described cosurfactant preferably is comprised of sorbitol and ethanol independent of one another, that separately use, and wherein, the weight proportion of sorbitol and ethanol is preferably 1-10: 0.5-2;
A kind of method for preparing above-mentioned microemulsion calcium-supplementing preparation comprises:
(1) takes by weighing each component by described weight portion;
The part of (2) taking out station its gross weight 5/1-2/1 from cosurfactant is mixed with surfactant, stirs water-bath; Add oil phase, water-bath is stirred, and gets mixed liquor I, and is for subsequent use;
(3) remaining cosurfactant and calcium source are dissolved in (consumption of distilled water is as long as fully dissolve sorbitol and calcium source in the distilled water, on this basis, more or a little lessly do not affect effect of the present invention), stir to clarify, get mixed liquor I I;
(4) mixed liquor I I is slowly added in the mixed liquor I, stir, and get final product;
Preferred, a kind of method for preparing above-mentioned microemulsion calcium-supplementing preparation comprises:
(1) takes by weighing each component by described weight portion;
(2) get soybean phospholipid and be dissolved in the ethanol, obtain soybean phospholipid-alcohol mixeding liquid, stir lower slowly add tween, water-bath; Add oil phase, water-bath is stirred, and gets mixed liquor I, and is for subsequent use;
(3) sorbitol and calcium source are dissolved in the distilled water (consumption of distilled water is as long as fully dissolve sorbitol and calcium source, on this basis, more or a little lessly do not affect effect of the present invention), stir to clarify, get mixed liquor I I;
(4) mixed liquor I I is slowly added in the mixed liquor I, stir, and get final product;
Wherein, the water-bath described in the step (2) preferably temperature is 30-50 ℃, more preferably 40 ℃ of water-baths;
The present invention is owing to adopted the oil phase of vitamin component (promotion calcium absorption) as microemulsion, lecithin etc. (having the effects such as blood fat reducing) component is as the surfactant of microemulsion, the components such as sorbitol (effect with correctives) are as the cosurfactant of microemulsion, can make on the one hand calcium preparation and promote the vitamin ingredients bag of calcium absorption to be loaded in the same system, vitamin is existed with liquid form, bring into play to greatest extent the effect that it promotes calcium absorption; Form on the other hand the various components of microemulsion structure simultaneously also as the component of the effects such as performance curative effect or taste masking, reduced supplementary product consumption.
Microemulsion calcium-supplementing preparation of the present invention is loaded in calcium preparation and vitamin ingredients bag in one individual system, is different from other the mode that simply the two suspendible (mixing) is prepared.Calcium only just can be absorbed in situation about existing with ion-type, is the aqueous solution of calcium gluconate such as the gluconic acid Ca oral liquid; And vitamin to form minute be the oiliness composition, simple suspendible is difficult to make profit to dissolve each other.And the essence of microemulsion is Emulsion, is altogether solution system of a kind of oil, water, and simultaneously, microemulsion is again a kind of special Emulsion, after being prepared into microemulsion, thermodynamics and kinetics all than emulsion stablize, degree of absorbing height, appearance looks elegant is transparent, preparation is simple.So, the invention provides the microemulsion calcium preparation method that comprises calcium preparation and vitamin component, be a kind of excellent vitamin calcium preparation.
Microemulsion calcium-supplementing preparation of the present invention can be prepared into food, health-care products, also it can be prepared into the medicine of prevention or the treatment disease relevant with calcium deficiency, can be according to further it being prepared into clinically acceptable suitable formulations, for example comprise the various preparations such as oral formulations, ejection preparation or transdermal absorption formulation.
The specific embodiment
Further describe the present invention below in conjunction with specific embodiment, advantage and disadvantage of the present invention will be more clear along with description.But these embodiment only are exemplary, scope of the present invention are not consisted of any restriction.It will be understood by those skilled in the art that lower without departing from the spirit and scope of the present invention and can make amendment or replace the details of technical solution of the present invention and form, but these modifications and replacing all fall within the scope of protection of the present invention.
The preparation of embodiment 1 microemulsion calcium-supplementing preparation
Take by weighing each component by following weight: tween 80 5g, soybean phospholipid 0.5g, sorbitol 1g, ethanol 0.5g, vitamin AD 1g, calcium gluconate 10g;
Soybean phospholipid is dissolved in the ethanol, stirs lower slowly add tween, 40 ℃ of water-baths; Add vitamin AD oil in above mixed liquor, 40 ℃ of water-baths are stirred, and get mixed liquor I, and are for subsequent use.Sorbitol and calcium gluconate are dissolved in an amount of distilled water, suitably heat (for example 30-50 ℃), stir to clarify, get mixed liquor I I.Mixed liquor I I is slowly added in the mixed liquor I, stir, get the clear micro-emulsion calcium.
The particle diameter that records prepared micro-emulsion calcium through the Ma Erwen laser granulometry is 15.4nm.
The preparation of embodiment 2 microemulsion calcium-supplementing preparations
Take by weighing each component by following weight: tween 80 20g, soybean phospholipid 2g, sorbitol 10g, ethanol 2g, vitamin AD 10g, calcium gluconate 50g;
Soybean phospholipid is dissolved in the ethanol, stirs lower slowly add tween, 40 ℃ of water-baths; Add vitamin AD oil in above mixed liquor, 40 ℃ of water-baths are stirred, and get mixed liquor I, and are for subsequent use.Sorbitol and calcium gluconate are dissolved in an amount of distilled water, suitably heat (for example 30-50 ℃), stir to clarify, get mixed liquor I I.Mixed liquor I I is slowly added in the mixed liquor I, stir, get the clear micro-emulsion calcium.
The particle diameter that records prepared micro-emulsion calcium through the Ma Erwen laser granulometry is 11.8nm.The preparation of embodiment 3 microemulsion calcium-supplementing preparations
Take by weighing each component by following weight: tween 80 10g, soybean phospholipid 1.5g, sorbitol 6g, ethanol 1.0g, vitamin AD 5g, calcium gluconate 25g;
Soybean phospholipid is dissolved in the ethanol, stirs lower slowly add tween, 40 ℃ of water-baths; Add vitamin AD oil in above mixed liquor, 40 ℃ of water-baths are stirred, and get mixed liquor I, and are for subsequent use.Sorbitol and calcium gluconate are dissolved in an amount of distilled water, suitably heat (for example 30-50 ℃), stir to clarify, get mixed liquor I I.Mixed liquor I I is slowly added in the mixed liquor I, stir, get the clear micro-emulsion calcium.
The particle diameter that records prepared micro-emulsion calcium through the Ma Erwen laser granulometry is 16.5nm.
Test example 1 micro-emulsion calcium of the present invention is on the impact of rat serum calcium concentration
One, test material:
1, laboratory animal: the wistar rat, male, 200-210g, Beijing Vital River Experimental Animals Technology Co., Ltd. provides, and the animal quality certification number is SCXK (capital) 2007-0001.
2, for the reagent thing: the prepared micro-emulsion calcium of embodiment 1-3,
3, control drug: gluconic acid Ca oral liquid (commercially available).
4, other reagent: Calcium, the safe clinical reagent company limited of Beijing Northization product, lot number: 080922.
Two, test method:
The 200-210g rat is divided into three groups at random by body weight, blank group, control drug group (gluconic acid Ca oral liquid), confession reagent thing group, 5 every group.Corresponding gavage gives medicine 10ml/kg respectively, and once a day, continuous 5 days, the blank group gave the distilled water of same volume.0.5h, 1h, 2h after the last administration get blood respectively at rat socket of the eye venous plexus, and be centrifugal, and separation of serum carries out the serum calcium levels measurement operation by the requirement of " Calcium " description.
Three, result of the test
Result of the test sees Table 1.
Table 1
Annotate: compare with the blank group,
*P＜0.05,
*P＜0.01
From result of the test as seen, 0.5h and 2h section are better than control drug group (commercially available calcium gluconate) for the serum calcium levels of reagent thing group.
Claims (10)
1. a microemulsion calcium-supplementing preparation is characterized in that: with the carrier of microemulsion structure as the calcium source; Wherein, the homogeneous system that formed by oil phase, water, surfactant and cosurfactant of described microemulsion structure; Wherein,
The weight portion of each component is: calcium source 10-50 weight portion, oil phase 1-10 weight portion, surfactant 5.5-22 weight portion, cosurfactant 1.5-12 weight portion;
Described oil phase is selected from vitamin A, vitamin D or vitamin AD;
Described calcium source is calcium gluconate;
Described surfactant is selected from one or more mixture that form in soybean phospholipid, lecithin, polyoxyethylene hydrogenated Oleum Ricini, tween 80 or the span;
Described cosurfactant is selected from one or more mixture that form in sorbitol, ethanol, glycerol or the glycerol.
2. according to microemulsion calcium-supplementing preparation claimed in claim 1, it is characterized in that: described surfactant is comprised of tween 80 and soybean phospholipid independent of one another, that separately use; Wherein, the weight proportion of tween 80 and soybean phospholipid is preferably 5-20:0.5-2; Described cosurfactant preferably is comprised of sorbitol and ethanol independent of one another, that separately use, and wherein, the weight proportion of sorbitol and ethanol is preferably 1-10:0.5-2.
3. according to microemulsion calcium-supplementing preparation claimed in claim 1, it is characterized in that, take by weighing each component by following weight: tween 80 5g, soybean phospholipid 0.5g, sorbitol 1g, ethanol 0.5g, vitamin AD 1g, calcium gluconate 10g;
Soybean phospholipid is dissolved in the ethanol, stirs lower slowly add tween, 40 ℃ of water-baths; Add vitamin AD oil in above mixed liquor, 40 ℃ of water-baths are stirred, and get the mixed liquor I, and are for subsequent use; Sorbitol and calcium gluconate are dissolved in an amount of distilled water, heat 30-50 ℃, stir to clarify, get the mixed liquor II; The mixed liquor II is slowly added in the mixed liquor I, stir, get the clear micro-emulsion calcium.
4. according to microemulsion calcium-supplementing preparation claimed in claim 1, it is characterized in that, take by weighing each component by following weight: tween 80 20g, soybean phospholipid 2g, sorbitol 10g, ethanol 2g, vitamin AD 10g, calcium gluconate 50g;
Soybean phospholipid is dissolved in the ethanol, stirs lower slowly add tween, 40 ℃ of water-baths; Add vitamin AD oil in above mixed liquor, 40 ℃ of water-baths are stirred, and get the mixed liquor I, and are for subsequent use; Sorbitol and calcium gluconate are dissolved in an amount of distilled water, heat 30-50 ℃, stir to clarify, get the mixed liquor II; The mixed liquor II is slowly added in the mixed liquor I, stir, get the clear micro-emulsion calcium.
5. according to microemulsion calcium-supplementing preparation claimed in claim 1, it is characterized in that, take by weighing each component by following weight: tween 80 10g, soybean phospholipid 1.5g, sorbitol 6g, ethanol 1.0g, vitamin AD 5g, calcium gluconate 25g;
Soybean phospholipid is dissolved in the ethanol, stirs lower slowly add tween, 40 ℃ of water-baths; Add vitamin AD oil in above mixed liquor, 40 ℃ of water-baths are stirred, and get the mixed liquor I, and are for subsequent use; Sorbitol and calcium gluconate are dissolved in an amount of distilled water, heat 30-50 ℃, stir to clarify, get the mixed liquor II; The mixed liquor II is slowly added in the mixed liquor I, stir, get the clear micro-emulsion calcium.
6. method for preparing the described microemulsion calcium-supplementing preparation of claim 1 comprises:
(1) takes by weighing each component by described weight portion;
(2) from cosurfactant, take out the part that accounts for its gross weight 5/1-2/1 and mix with surfactant, stir water-bath; Add oil phase, water-bath is stirred, and gets the mixed liquor I, and is for subsequent use;
(3) remaining cosurfactant and calcium source are dissolved in the distilled water, stir to clarify, get the mixed liquor II;
(4) the mixed liquor II is slowly added in the mixed liquor I, stir, and get final product.
7. method for preparing the described microemulsion calcium-supplementing preparation of claim 2 comprises:
(1) takes by weighing each component by described weight portion;
(2) get soybean phospholipid and be dissolved in the ethanol, obtain soybean phospholipid-alcohol mixeding liquid, stir lower slowly add tween, water-bath; Add oil phase, water-bath is stirred, and gets the mixed liquor I, and is for subsequent use;
(3) sorbitol and calcium source are dissolved in the distilled water, stir to clarify, get the mixed liquor II;
(4) the mixed liquor II is slowly added in the mixed liquor I, stir, and get final product.
8. according to claim 6 or 7 described methods, it is characterized in that: the bath temperature described in the step (2) is 30-50 ℃.
9. it is characterized in that in accordance with the method for claim 8: the bath temperature described in the step (2) is 40 ℃.
10. the purposes of any one described microemulsion calcium-supplementing preparation of claim 1-5 in preparation prevention or the treatment disease medicament relevant with calcium deficiency.
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| CN105616441B (en) * | 2014-11-05 | 2018-08-14 | 澳美制药厂有限公司 | Calcichew D3 piece and preparation method thereof |
| CN105768109A (en) * | 2016-02-25 | 2016-07-20 | 李宏 | Vitamin D and calcium-containing microemulsion as well as preparation method and application thereof |
| CN107129352A (en) * | 2017-04-27 | 2017-09-05 | 广西棕海园林工程有限公司 | Calcium in Plants |
| CN111481503B (en) * | 2020-04-09 | 2022-03-04 | 暨南大学 | Vitamin D3-loaded nano calcium carbonate pickering emulsion and preparation method and application thereof |
| CN114732092A (en) * | 2022-04-21 | 2022-07-12 | 清远金沣生物药品有限公司 | Active calcium and magnesium microemulsion and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1439298A (en) * | 2003-03-18 | 2003-09-03 | 华瑞制药有限公司 | Cellulosefree intestinal absorbing nutrient emulsion and its preparing method |
| CN1562044A (en) * | 2004-04-12 | 2005-01-12 | 沈阳药科大学 | Witamin D2 calcium levulinate freeze-dried emulsion and its preparing method |
| CN101006822A (en) * | 2007-02-05 | 2007-08-01 | 熊旭华 | Cartoon powdered ice cream containing vitamin A, D and calcium |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1439298A (en) * | 2003-03-18 | 2003-09-03 | 华瑞制药有限公司 | Cellulosefree intestinal absorbing nutrient emulsion and its preparing method |
| CN1562044A (en) * | 2004-04-12 | 2005-01-12 | 沈阳药科大学 | Witamin D2 calcium levulinate freeze-dried emulsion and its preparing method |
| CN101006822A (en) * | 2007-02-05 | 2007-08-01 | 熊旭华 | Cartoon powdered ice cream containing vitamin A, D and calcium |
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