CN109498590B - Lactoferrin capsule and preparation method thereof - Google Patents
Lactoferrin capsule and preparation method thereof Download PDFInfo
- Publication number
- CN109498590B CN109498590B CN201811454395.7A CN201811454395A CN109498590B CN 109498590 B CN109498590 B CN 109498590B CN 201811454395 A CN201811454395 A CN 201811454395A CN 109498590 B CN109498590 B CN 109498590B
- Authority
- CN
- China
- Prior art keywords
- lactoferrin
- parts
- solution
- stirring
- lithocholic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/26—Iron; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
Abstract
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a lactoferrin capsule and a preparation method thereof, wherein the lactoferrin capsule comprises the following raw materials in parts by weight: 10-15 parts of lactoferrin; 3-6 parts of ferrous gluconate; 7-9 parts of corn starch; 1-4 parts of magnesium stearate; 5-9 parts of alpha-cyclodextrin; 4-6 parts of lithocholic acid; the lactoferrin capsule has high-quality thermal stability and storage stability under the synergistic effect of ferrous gluconate, lithocholic acid and alpha-cyclodextrin, can be subjected to high-temperature sterilization at 100 ℃, more than 95% of lactoferrin is not denatured, and the lactoferrin capsule is stored for more than 6 months at normal temperature, and more than 99% of lactoferrin is not denatured.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a lactoferrin capsule and a preparation method thereof.
Background
Lactoferrin, also known as lactoferrin, is a glycoprotein capable of binding iron, a species of ferritin, the main body of the molecule being composed of about 700 amino acid residues; lactoferrin is one of 4 major proteins in human milk, accounting for about 20% of the total protein in human milk, and has at least two aspects of its nutritional value: the dietary protein source is used as the dietary protein source of amino acid, and the biological utilization of iron is facilitated. The lactoferrin can be reversibly bound with iron in a high-affinity manner through two iron binding regions at the amino terminal and the carboxyl terminal of the lactoferrin, and the iron element is maintained in a wider pH value range to complete the absorption and utilization of iron in duodenal cells; lactoferrin plays an important role as an iron transport carrier in the iron absorption process.
Chinese patent CN106075411A discloses a preparation method of a natural iron-supplementing soft capsule, which comprises lactoferrin, ferrous gluconate, vitamin C, salad oil, white atractylodes rhizome powder and roasted liquorice powder, can improve the treatment effect of iron-deficiency anemia, and has no adverse reaction in gastrointestinal tract; but lactoferrin as a pharmaceutical preparation often needs to be heat sterilized to prolong the shelf life; lactoferrin has poor thermal stability, can improve the thermal stability of lactoferrin by being compounded with ferrous gluconate, but can shorten the storage time of lactoferrin, is easy to find deformation after being stored for a long time, and influences the using effect of lactoferrin.
Disclosure of Invention
The invention solves the technical problems in the prior art and provides a lactoferrin capsule and a preparation method thereof.
In order to solve the problems, the technical scheme of the invention is as follows:
a lactoferrin capsule comprises the following raw materials in parts by weight:
10-15 parts of lactoferrin;
3-6 parts of ferrous gluconate;
7-9 parts of corn starch;
1-4 parts of magnesium stearate;
5-9 parts of alpha-cyclodextrin;
lithocholic acid, 4-6 parts.
A preparation method of a lactoferrin capsule comprises the following steps:
step 1, mixing alpha-cyclodextrin with water, heating to 70-90 ℃, adding ferrous gluconate, stirring and heating, and keeping the temperature at 100 ℃ to prepare a solution A;
dissolving lithocholic acid in DMSO (dimethyl sulfoxide), adding EDC (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) and NHS (N-hydroxysuccinimide), and stirring to prepare a solution B;
step 3, cooling the solution A to 30-40 ℃, dropwise adding the solution B into the solution A under the stirring condition, keeping the temperature, and continuously stirring to prepare a solution C;
step 4, adding lactoferrin into the solution C under the condition of stirring, stirring for a period of time at the temperature of 30-40 ℃, removing the solvent, and drying to obtain solid powder;
and 5, uniformly mixing the solid powder prepared in the step 4 with corn starch and magnesium stearate, and heating and sterilizing to prepare the lactoferrin capsule.
Preferably, the mass fraction of the alpha-cyclodextrin in the solution A is 0.5-0.9%.
Preferably, the mass fraction of lithocholic acid in the solution B is 4-6%; the molar ratio of lithocholic acid to EDC to NHS is 1:1: 1.
Preferably, the stirring time of the step 1 is 3 to 4 hours.
Preferably, the stirring time of the step 2 is 2 to 3 hours.
Preferably, the stirring time of the step 3 is 6 to 8 hours.
Preferably, the stirring time of the step 4 is 6 to 8 hours.
Preferably, the step 1-4 stirring speed is 400-1000 rpm.
Preferably, the heat sterilization conditions in the step 5 are as follows: 100 ℃ for 2 hours.
Compared with the prior art, the invention has the advantages that,
the lactoferrin capsule has high-quality thermal stability and storage stability under the synergistic effect of ferrous gluconate, lithocholic acid and alpha-cyclodextrin, can be subjected to high-temperature sterilization at 100 ℃, more than 95% of lactoferrin is not denatured, the lactoferrin capsule is stored for more than 6 months at normal temperature, and more than 99% of lactoferrin is not denatured;
according to the preparation method of the lactoferrin capsule, EDC and NHS are selected to organically combine lithocholic acid, ferrous gluconate and the lactoferrin capsule, and the final product has good thermal stability and storage stability, and is simple in preparation process and low in cost.
Detailed Description
Example 1:
a lactoferrin capsule comprises the following raw materials in parts by weight:
10 parts of lactoferrin;
3 parts of ferrous gluconate;
7 parts of corn starch;
magnesium stearate, 1 part;
5 parts of alpha-cyclodextrin;
lithocholic acid, 4 parts.
The preparation method of the lactoferrin capsule comprises the following steps:
step 1, mixing alpha-cyclodextrin with water, heating to 70-90 ℃, adding ferrous gluconate, stirring and heating for 3-4 hours, and keeping the temperature at 100 ℃ to prepare a solution A; the mass fraction of the alpha-cyclodextrin in the solution A is 0.5 percent;
step 2, dissolving lithocholic acid in dimethyl sulfoxide DMSO, adding EDC (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) and NHS (N-hydroxysuccinimide), and stirring for 2-3 hours to prepare a solution B; the mass fraction of lithocholic acid in the solution B is 4%; the molar ratio of lithocholic acid to EDC to NHS is 1:1: 1;
step 3, cooling the solution A to 30-40 ℃, dropwise adding the solution B into the solution A under the stirring condition, keeping the temperature, and continuously stirring for 6-8 hours to prepare a solution C;
step 4, adding lactoferrin into the solution C under the condition of stirring, stirring for 6-8 hours at the temperature of 30-40 ℃, removing the solvent, and drying to obtain solid powder;
and 5, uniformly mixing the solid powder prepared in the step 4 with corn starch and magnesium stearate, and heating and sterilizing at 100 ℃ for 2 hours to prepare the lactoferrin capsule.
The stirring speed in steps 1-4 is generally selected to be 400-.
Example 2:
a lactoferrin capsule comprises the following raw materials in parts by weight:
12 parts of lactoferrin;
4 parts of ferrous gluconate;
8 parts of corn starch;
magnesium stearate, 2 parts;
7 parts of alpha-cyclodextrin;
lithocholic acid, 5 parts.
The preparation method of the lactoferrin capsule comprises the following steps:
step 1, mixing alpha-cyclodextrin with water, heating to 70-90 ℃, adding ferrous gluconate, stirring and heating for 3-4 hours, and keeping the temperature at 100 ℃ to prepare a solution A; the mass fraction of the alpha-cyclodextrin in the solution A is 0.7 percent;
step 2, dissolving lithocholic acid in dimethyl sulfoxide DMSO, adding EDC (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) and NHS (N-hydroxysuccinimide), and stirring for 2-3 hours to prepare a solution B; the mass fraction of lithocholic acid in the solution B is 5%; the molar ratio of lithocholic acid to EDC to NHS is 1:1: 1;
step 3, cooling the solution A to 30-40 ℃, dropwise adding the solution B into the solution A under the stirring condition, keeping the temperature, and continuously stirring for 6-8 hours to prepare a solution C;
step 4, adding lactoferrin into the solution C under the condition of stirring, stirring for 6-8 hours at the temperature of 30-40 ℃, removing the solvent, and drying to obtain solid powder;
and 5, uniformly mixing the solid powder prepared in the step 4 with corn starch and magnesium stearate, and heating and sterilizing at 100 ℃ for 2 hours to prepare the lactoferrin capsule.
The stirring speed in steps 1-4 is generally selected to be 400-.
Example 3:
a lactoferrin capsule comprises the following raw materials in parts by weight:
15 parts of lactoferrin;
6 parts of ferrous gluconate;
9 parts of corn starch;
magnesium stearate, 4 parts;
9 parts of alpha-cyclodextrin;
lithocholic acid, 6 parts.
The preparation method of the lactoferrin capsule comprises the following steps:
step 1, mixing alpha-cyclodextrin with water, heating to 70-90 ℃, adding ferrous gluconate, stirring and heating for 3-4 hours, and keeping the temperature at 100 ℃ to prepare a solution A; the mass fraction of the alpha-cyclodextrin in the solution A is 0.9 percent;
step 2, dissolving lithocholic acid in dimethyl sulfoxide DMSO, adding EDC (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) and NHS (N-hydroxysuccinimide), and stirring for 2-3 hours to prepare a solution B; the mass fraction of lithocholic acid in the solution B is 6%; the molar ratio of lithocholic acid to EDC to NHS is 1:1: 1;
step 3, cooling the solution A to 30-40 ℃, dropwise adding the solution B into the solution A under the stirring condition, keeping the temperature, and continuously stirring for 6-8 hours to prepare a solution C;
step 4, adding lactoferrin into the solution C under the condition of stirring, stirring for 6-8 hours at the temperature of 30-40 ℃, removing the solvent, and drying to obtain solid powder;
and 5, uniformly mixing the solid powder prepared in the step 4 with corn starch and magnesium stearate, and heating and sterilizing at 100 ℃ for 2 hours to prepare the lactoferrin capsule.
The stirring speed in steps 1-4 is generally selected to be 400-.
Comparative example 1:
lactoferrin capsules were prepared as in example 2, except that lithocholic acid was added in the following amounts:
group A: 1 part of lithocholic acid; the mass fraction of lithocholic acid in the solution B is 1%;
group B: lithocholic acid, 10 parts; the mass fraction of lithocholic acid in the solution B is 10%.
Comparative example 2:
lactoferrin capsules were prepared as in example 2, except that the α -cyclodextrin was replaced by:
group A: a beta-cyclic paste;
group B: gamma-cyclic paste.
Example 4:
examination of thermal stability and storage stability
The heat stability is expressed by the percentage of the undenatured lactoferrin amount in the product to the original added mass of lactoferrin;
the storage stability of the product is that the amount of undenatured lactoferrin accounts for the percentage of the amount of undenatured lactoferrin in the fresh product after the product is stored for 6 months at normal temperature;
the results of examining the products of examples 1-3 and comparative examples 1-2 are shown in the following table:
| group of | Thermal stability% | Storage stability% |
| Example 1 | 93.5 | 98.3 |
| Example 2 | 95.1 | 99.4 |
| Example 3 | 94.3 | 97.6 |
| Comparative example 1 group A | 74.2 | 34.2 |
| Comparative example 1 group B | 90.7 | 37.8 |
| Comparative example 2 group A | 81.6 | 90.6 |
| Comparative example 2 group B | 76.5 | 89.1 |
As can be seen from the above table, the addition amount of lithocholic acid should not be too low, otherwise, the thermal stability and storage stability of the product are greatly affected; meanwhile, the addition amount of lithocholic acid is not suitable to be too high, otherwise, the lithocholic acid has good thermal stability but poor storage stability;
the addition of beta-cyclodextrin and gamma-cyclodextrin has certain help to the heat stability and storage stability of the product, but the effect is not as good as that of alpha-cyclodextrin.
It should be noted that the above-mentioned embodiments are only preferred embodiments of the present invention, and are not intended to limit the scope of the present invention, and all equivalent substitutions or substitutions made on the above-mentioned embodiments are included in the scope of the present invention.
Claims (9)
1. The lactoferrin capsule is characterized by comprising the following raw materials in parts by weight:
10-15 parts of lactoferrin;
3-6 parts of ferrous gluconate;
7-9 parts of corn starch;
1-4 parts of magnesium stearate;
5-9 parts of alpha-cyclodextrin;
4-6 parts of lithocholic acid;
the preparation method of the lactoferrin capsule comprises the following steps:
step 1, mixing alpha-cyclodextrin with water, heating to 70-90 ℃, adding ferrous gluconate, stirring and heating, and keeping the temperature at 100 ℃ to prepare a solution A;
step 2, dissolving lithocholic acid in DMSO, adding EDC and NHS, and stirring to prepare a solution B;
step 3, cooling the solution A to 30-40 ℃, dropwise adding the solution B into the solution A under the stirring condition, keeping the temperature, and continuously stirring to prepare a solution C;
step 4, adding lactoferrin into the solution C under the condition of stirring, stirring for a period of time at the temperature of 30-40 ℃, removing the solvent, and drying to obtain solid powder;
and 5, uniformly mixing the solid powder prepared in the step 4 with corn starch and magnesium stearate, and heating and sterilizing to prepare the lactoferrin capsule.
2. Lactoferrin capsule according to claim 1, characterized in that the mass fraction of α -cyclodextrin in solution A is comprised between 0.5 and 0.9%.
3. The lactoferrin capsule of claim 1, wherein the mass fraction of lithocholic acid in solution B is 4-6%; the molar ratio of lithocholic acid to EDC to NHS is 1:1: 1.
4. A lactoferrin capsule according to claim 1, wherein the stirring time of step 1 is 3-4 hours.
5. A lactoferrin capsule according to claim 1, wherein the stirring time of step 2 is 2-3 hours.
6. A lactoferrin capsule according to claim 1, wherein the stirring time of step 3 is 6-8 hours.
7. A lactoferrin capsule according to claim 1, wherein the stirring time of step 4 is 6-8 hours.
8. Lactoferrin capsule according to claim 1, characterized in that the stirring speed in steps 1-4 is 400-1000 rpm.
9. A lactoferrin capsule according to claim 1, wherein the conditions for heat sterilization in step 5 are: 100 ℃ for 2 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811454395.7A CN109498590B (en) | 2018-11-30 | 2018-11-30 | Lactoferrin capsule and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811454395.7A CN109498590B (en) | 2018-11-30 | 2018-11-30 | Lactoferrin capsule and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109498590A CN109498590A (en) | 2019-03-22 |
| CN109498590B true CN109498590B (en) | 2021-06-22 |
Family
ID=65749923
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811454395.7A Active CN109498590B (en) | 2018-11-30 | 2018-11-30 | Lactoferrin capsule and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109498590B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115025101A (en) * | 2022-06-29 | 2022-09-09 | 扬州大学 | Lithocholic acid-added medicament for preventing and treating mycotoxin poisoning and preparation method and application thereof |
| CN117159702A (en) * | 2023-09-19 | 2023-12-05 | 广州见华医学科技有限公司 | Application of lactoferrin capsule in regulating human immunity |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101711873A (en) * | 2008-10-06 | 2010-05-26 | 中国科学院大连化学物理研究所 | Method for preparing amphiphilic chitosan nanometer medicament carrier |
| CN106075411A (en) * | 2016-07-12 | 2016-11-09 | 方雅悯 | A kind of preparation method of natural iron supplement soft capsule |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030190355A1 (en) * | 2002-04-05 | 2003-10-09 | Hermelin Marc S. | Modified release minerals |
-
2018
- 2018-11-30 CN CN201811454395.7A patent/CN109498590B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101711873A (en) * | 2008-10-06 | 2010-05-26 | 中国科学院大连化学物理研究所 | Method for preparing amphiphilic chitosan nanometer medicament carrier |
| CN106075411A (en) * | 2016-07-12 | 2016-11-09 | 方雅悯 | A kind of preparation method of natural iron supplement soft capsule |
Non-Patent Citations (1)
| Title |
|---|
| 《EDC/NHS交联对胶原物理化学性能的影响》，王迎军等，华南理工大学学报（自然科学版），第35卷第12期，第66-70页;王迎军等;《华南理工大学学报（自然科学版）》;20071231;第35卷(第12期);第66-70页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109498590A (en) | 2019-03-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sun et al. | Recent advances in protein–polyphenol interactions focusing on structural properties related to antioxidant activities | |
| Shanthakumar et al. | The current situation of pea protein and its application in the food industry | |
| US9828439B2 (en) | Hybrid vegetable protein and method for obtaining same | |
| CN109498590B (en) | Lactoferrin capsule and preparation method thereof | |
| CN1104890A (en) | Cation-complexed polysacharides | |
| Lei et al. | The effect of deamidation on the structural, functional, and rheological properties of glutelin prepared from Akebia trifoliata var. australis seed | |
| Wang et al. | Improving myofibrillar proteins solubility and thermostability in low-ionic strength solution: A review | |
| DE2405589A1 (en) | PROCESS FOR MANUFACTURING PROTEIN CONTAINING FOOD ADDITIVES | |
| JPS58159421A (en) | Biologically available iron derivatives without stomach injury, manufacture and medicine | |
| KR20200030779A (en) | Chelate collagen peptide and method for preparing the same | |
| Guo et al. | Examination of the causes of instability of soy protein isolate during storage through probing of the heat-induced aggregation | |
| Polidori et al. | Differences of protein fractions among fresh, frozen and powdered donkey milk | |
| Cao et al. | Effect of conventional and microwave heating treatment on antioxidant activity of quinoa protein after simulated gastrointestinal digestion | |
| Chima et al. | Physicochemical Characterization of Interactions between Blueberry Polyphenols and Food Proteins from Dairy and Plant Sources | |
| JP2006526418A (en) | Beverage additive mixture of trehalose and protein | |
| Zhang et al. | Protein aggregation impacts in vitro protein digestibility, peptide profiling and potential bioactive peptides of soymilk and dry-heated soybeans | |
| CN110584069A (en) | Green and healthy oyster sauce | |
| KR101093170B1 (en) | Manufacturing method of Baekseolgi adding of whey protein concentrates | |
| CN112823645A (en) | Dairy product and preparation method thereof | |
| US7264839B2 (en) | Protein beverage | |
| Bebartta et al. | Development of cryo‐desiccated whey and soy protein conglomerates; effect of maltodextrin on their functionality and digestibility | |
| JP2015134753A (en) | collagen peptide complex | |
| JP2005040128A (en) | Biological method for obtaining food modifier based on heme iron, and food modifier to be obtained by the method | |
| CN105941821A (en) | Method for preparing oat globulin acidic gel | |
| JP7040898B2 (en) | Oral composition for promoting type III collagen production containing a hydrolyzed eggshell membrane component as an active ingredient |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |