High-bioavailability frankincense extract preparation and preparation method thereof

Abstract

The invention discloses a frankincense extract preparation with high bioavailability and a preparation method thereof, and relates to the field of traditional Chinese medicine preparations. The preparation method comprises the following steps: reacting frankincense extract with povidone at a specific ratio to prepare a solid dispersion, and reacting with phospholipid to form a phospholipid complex; the dissolution rates of the main functional components 3-acetyl-11-carbonyl-beta-masticinic acid (AKBA) and 11-carbonyl-beta-masticinic acid (KBA) of the obtained frankincense extract preparation are greatly improved, and the dissolution rate of the KBA can be up to 100%; moreover, the frankincense extract has good dispersibility in water, and can be applied to tablets, capsules and other finished product dosage forms, so that the application range of the frankincense extract is expanded.

Description

Technical Field

[0001] The invention relates to the field of traditional Chinese medicine preparations, and in particular to a frankincense extract preparation with high solubility and a preparation method thereof. Background Art

[0002] Frankincense is a traditional Chinese medicinal material with a wide range of pharmacological effects. Modern pharmacological studies have shown that frankincense has anti-inflammatory, analgesic, anti-asthmatic, antioxidant, liver-protecting, and cholesterol synthesis-inhibiting activities. The active ingredients of frankincense are also relatively rich. The active ingredients currently isolated from frankincense include terpenes, volatile oils, sugars, sterols, etc. The main active ingredients of frankincense extracts are triterpene acid compounds such as pentacyclic triterpenes and tetracyclic triterpenes. A large number of studies have shown that frankincense triterpene acid compounds have anti-inflammatory and anti-rheumatic effects, and have good effects in treating induced arthritis. Among the frankincense triterpene acid compounds, 3-acetyl-11-carbonyl-β-boswellic acid (AKBA) and 11-carbonyl-β-boswellic acid (KBA) have the highest content and the strongest efficacy, but frankincense extracts are lipophilic substances with extremely poor water solubility and are almost insoluble in water, so their bioavailability is also poor. It is crucial to improve the water solubility of frankincense extracts and increase their in vivo bioavailability.

[0003] Among the products currently on the market, some have prepared frankincense extracts into phospholipid complexes to improve their bioavailability. Studies have shown that when the ratio of frankincense extract: phospholipid: microcrystalline cellulose is 1:1:2, the phospholipid complex can increase the bioavailability of AKBA by about 2 times. The water solubility of the product was tested, and the experimental results showed that the solubility of AKBA was 31.21% and the solubility of KBA was 32.82%, which was improved but not high. In addition, the content of AKBA, the main active ingredient in the product, was low, only 1.5%. Summary of the invention

[0004] The purpose of the present invention is to provide a highly water-soluble frankincense extract preparation technology and a preparation method thereof, to improve the water solubility and bioavailability of the frankincense extract by means of preparation, and to prepare a product with a high AKBA content, so as to facilitate the wide application of the frankincense extract, and to provide the possibility of other dosage forms of the related finished products.

[0005] In a first aspect, the present invention provides a frankincense extract preparation with high bioavailability, comprising a frankincense extract, a solid dispersion carrier material and a phospholipid, wherein the ratio of the mass of the frankincense extract to the total mass of the solid dispersion carrier material and the phospholipid is 1:1-3, specifically 1:1, 1:1.5, 1:2, 1:2.5, 1:3.

[0006] In some embodiments, the ratio of the mass of frankincense extract to the total mass of the solid dispersion carrier material and the phospholipid is 1:2.

[0007] In some embodiments, the mass of the solid dispersion carrier material accounts for 10%-65% of the total mass of the solid dispersion carrier material and the phospholipid.

[0008] In some embodiments, the mass of the solid dispersion carrier material accounts for 25%-50% of the total mass of the solid dispersion carrier material and the phospholipid.

[0009] In some embodiments, the solid dispersion carrier material is a water-soluble carrier material.

[0010] In some embodiments, the water-soluble carrier material is a polyvinyl pyrrolidone.

[0011] In some embodiments, polyvinyl pyrrolidones include, but are not limited to, one or a combination of povidone K30, povidone K15, and povidone K90.

[0012] In some embodiments, the source of phospholipids is soybean lecithin, sunflower lecithin or egg yolk lecithin, or a combination thereof.

[0013] In some embodiments, the content of phosphatidylcholine in the phospholipids is 40%-90%.

[0014] In some embodiments, the content of phosphatidylcholine in the phospholipids is 50%-80%.

[0015] In a second aspect, the present invention provides a method for preparing a frankincense extract preparation, comprising adding a frankincense extract and a carrier material of a solid dispersion into an organic solvent, heating and stirring; after the reaction is completed, adding phospholipids, continuing heating and stirring, concentrating and drying to obtain a product.

[0016] In some embodiments, the organic solvent includes, but is not limited to, one or more combinations of methanol, anhydrous ethanol, acetone, and ethyl acetate.

[0017] In some embodiments, the organic solvent is ethanol.

[0018] In some embodiments, the volume ratio of the total mass of the frankincense extract, the carrier material of the solid dispersion and the phospholipid to the organic solvent is 1 g: 1-9 mL.

[0019] In some embodiments, the volume ratio of the total mass of frankincense extract, carrier material of the solid dispersion and phospholipids to the organic solvent is 1g:3-7mL, specifically 1g:3mL, 1g:4mL, 1g:5mL, 1g:6mL, 1g:7mL.

[0020] In some embodiments, the preparation method of the frankincense extract preparation is to add the frankincense extract and the carrier material of the solid dispersion into an organic solvent, heat to completely dissolve, and then stir and react at a certain temperature to obtain a frankincense extract solid dispersion; after the reaction is completed, phospholipids are added to completely dissolve it, and the stirring reaction is continued at a certain temperature. After the reaction is completed, the crude product is obtained by vacuum concentration and drying to remove anhydrous ethanol, and then crushing and sieving to obtain the final product.

[0021] In some embodiments, the reaction temperature of the frankincense extract and the solid dispersion carrier material in the preparation method is 60-120°C, specifically 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, 120°C.

[0022] In some embodiments, the heating and stirring time of the frankincense extract and the solid dispersion carrier material in the preparation method is 1-5 hours, specifically 1 hour, 2 hours, 3 hours, 4 hours, 5 hours.

[0023] In some embodiments, the reaction temperature of the frankincense extract solid dispersion and phospholipids in the preparation method is 30-70°C, specifically 30°C, 40°C, 50°C, 60°C, 70°C.

[0024] In some embodiments, the reaction time of the frankincense extract solid dispersion and the phospholipid in the preparation method is 0.5-3 h, specifically 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h.

[0025] In a third aspect, a method is provided for preparing anti-inflammatory, analgesic, anti-asthmatic, antioxidant, and liver disease-protecting medicines, health foods, dietary supplements, and / or foods using the above-mentioned frankincense extract preparation and the frankincense extract preparation obtained by the preparation method.

[0026] Beneficial effects:

[0027] The preparation method of the present invention comprises the following steps: firstly reacting the frankincense extract with polyvidone in a specific ratio to prepare a solid dispersion, and then reacting the frankincense extract with phospholipids to form a phospholipid complex; the solubility of the main effective ingredients of the obtained frankincense extract preparation, 3-acetyl-11-carbonyl-β-boswellic acid (AKBA) and 11-carbonyl-β-boswellic acid (KBA), is greatly improved, and the solubility of KBA can reach up to 100%; and the frankincense extract has good dispersibility in water, and can be applied to tablets, capsules and other finished dosage forms, thereby expanding the application range of the frankincense extract. DETAILED DESCRIPTION

[0029] In order to facilitate the understanding of those skilled in the art, the present invention is further described below in conjunction with embodiments, and the contents mentioned in the implementation modes are not intended to limit the present invention.

[0030] In the following examples, the total mass of frankincense extract, povidone and phospholipids is 30 g.

[0031] Example 1

[0032] The raw materials and auxiliary materials are weighed in a ratio of frankincense extract: povidone K30: phospholipid (PC 80%) = 2:1:3. The specific preparation method is to add frankincense extract and povidone K30 into 150mL of anhydrous ethanol, heat until completely dissolved, and stir at 90°C for 3h; after the reaction, add phospholipid and stir until completely dissolved, stir at 50°C for 1h, and after the reaction, vacuum concentrate and dry to remove anhydrous ethanol to obtain a crude product, crush the crude product and pass it through an 80-mesh sieve to obtain the final product and test its solubility. The AKBA content of the obtained product is 10.05%, the solubility of the main active ingredient AKBA is 50.70%, and the solubility of KBA is 50.76%.

[0033] Example 2

[0034] The raw materials and auxiliary materials were weighed in a ratio of frankincense extract: povidone K30: phospholipid (PC 50%) = 2:1:3. The specific preparation method was as follows: the frankincense extract and povidone K30 were added to 150 mL of anhydrous ethanol, heated until completely dissolved, and stirred at 90°C for 3 hours; after the reaction, the phospholipid was added and stirred until completely dissolved, and stirred at 50°C for 1 hour. After the reaction, the anhydrous ethanol was removed by vacuum concentration and drying to obtain a crude product, and the crude product was crushed and sieved through an 80-mesh sieve to obtain the final product and its solubility was tested. The AKBA content of the obtained product was 11.50%, the solubility of the main active ingredient AKBA was 35.92%, and the solubility of KBA was 38.85%.

[0035] Example 3

[0036] The raw materials and auxiliary materials are weighed in a ratio of frankincense extract: povidone K30: phospholipid (PC 80%) = 1:1:1. The specific preparation method is to add frankincense extract and povidone K30 into 150mL of anhydrous ethanol, heat until completely dissolved, and stir at 90°C for 3h; after the reaction, add phospholipid and stir until completely dissolved, stir at 50°C for 1h, and after the reaction, vacuum concentrate and dry to remove anhydrous ethanol to obtain a crude product, crush the crude product and pass it through an 80-mesh sieve to obtain the final product and test its solubility. The AKBA content of the obtained product is 11.50%, the solubility of the main active ingredient AKBA is 30.76%, and the solubility of KBA is 33.68%.

[0037] Example 4

[0038] The raw materials and auxiliary materials were weighed in a ratio of frankincense extract: povidone K30: phospholipid (PC 80%) = 5:3:7. The specific preparation method was as follows: the frankincense extract and povidone K30 were added to 150 mL of anhydrous ethanol, heated until completely dissolved, and stirred at 90°C for 3 hours; after the reaction, the phospholipid was added and stirred until completely dissolved, and stirred at 50°C for 1 hour. After the reaction, the anhydrous ethanol was removed by vacuum concentration and drying to obtain a crude product, and the crude product was crushed and sieved through an 80-mesh sieve to obtain the final product and its solubility was tested. The AKBA content of the obtained product was 16.62%, the solubility of the main active ingredient AKBA was 66.34%, and the solubility of KBA was 95.28%.

[0039] Example 5

[0040] The raw materials and auxiliary materials were weighed in a ratio of frankincense extract: povidone K15: phospholipid (PC 80%) = 5:3:7. The specific preparation method was as follows: the frankincense extract and povidone K15 were added to 150 mL of anhydrous ethanol, heated until completely dissolved, and stirred at 90°C for 3 hours; after the reaction, the phospholipid was added and stirred until completely dissolved, and stirred at 50°C for 1 hour. After the reaction, the anhydrous ethanol was removed by vacuum concentration and drying to obtain a crude product, and the crude product was crushed and sieved through an 80-mesh sieve to obtain the final product and its solubility was tested. The AKBA content of the obtained product was 11.70%, the solubility of the main active ingredient AKBA was 67.34%, and the solubility of KBA was 100.00%.

[0041] Comparative Example 1

[0042] According to the ratio of frankincense extract: povidone K30: γ-cyclodextrin = 1:1:1, add frankincense extract and povidone K30 according to the formula to 150mL anhydrous ethanol, react at 60℃ for 1h, add γ-cyclodextrin according to the formula, react at 60℃ for 1h, vacuum concentrate and dry to remove anhydrous ethanol after the reaction to obtain a crude product, crush the crude product and pass it through an 80-mesh sieve to obtain the final product, and test its solubility. The AKBA content of the obtained product is 11.2%, the solubility of the main active ingredient AKBA is 10.64%, and the solubility of KBA is 38.31%.

[0043] Comparative Example 2

[0044] The raw materials and auxiliary materials are weighed in a ratio of frankincense extract: phospholipid (PC 80%): microcrystalline cellulose = 1:1:1. The specific preparation method is to add the frankincense extract and phospholipid (PC 80%) into anhydrous ethanol, heat until completely dissolved, and stir and react at 60°C for 2 hours; after the reaction, add microcrystalline cellulose, stir and react at 60°C for 1 hour, and after the reaction, vacuum concentrate and dry to remove anhydrous ethanol to obtain a crude product, crush the crude product, pass it through an 80-mesh sieve to obtain the final product, and test its solubility. The AKBA content of the obtained product is 11.80%, the solubility of the main active ingredient AKBA is 30.76%, and the solubility of KBA is 33.68%.

[0045] Comparison revealed that in the two-step reaction, after the phospholipid was replaced by γ-cyclodextrin in Comparative Example 1 and the povidone was replaced by microcrystalline cellulose in Comparative Example 2, the solubility was greatly reduced compared with that in the examples, which indicates that the composition of the present invention brings unexpected technical effects.

[0046] The dissolution determination method of AKBA and KBA in the above examples and comparative examples is as follows:

[0047] Dissolution method, specific steps:

[0048] 1. Preheat the dissolution apparatus to 37°C.

[0049] 2. Fill the dissolution apparatus with pH 7.2 PBS buffer and preheat to 37°C.

[0050] 3. Add sample and stir to dissolve (250r / min).

[0051] 4. Take 1h sample.

[0052] 5. Liquid phase detection content.

[0053] It should be understood that the detailed description of the technical solutions of the present invention by means of the preferred embodiments is illustrative rather than restrictive. A person skilled in the art may modify the technical solutions described in the embodiments, or replace some of the technical features by equivalents, based on reading the specification of the present invention; and these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A frankincense extract preparation with high bioavailability, characterized in that: The invention comprises frankincense extract, a solid dispersion carrier material and phospholipids, wherein the mass ratio of the frankincense extract to the total mass ratio of the solid dispersion carrier material and the phospholipids is 1:1-3.

2. The preparation according to claim 1, characterized in that The mass ratio of the frankincense extract to the total mass of the solid dispersion carrier material and the phospholipid is 1:

2.

3. The preparation according to any one of claims 1 to 2, characterized in that The mass ratio of the solid dispersion carrier material to the total mass of the solid dispersion carrier material and the phospholipid is 10%-65%.

4. The preparation according to claim 3, characterized in that The mass ratio of the solid dispersion carrier material to the total mass of the solid dispersion carrier material and the phospholipid is 25%-50%.

5. The preparation according to claim 4, characterized in that The solid dispersion carrier material is a water-soluble carrier material.

6. The preparation according to claim 5, characterized in that The water-soluble carrier material is polyvinyl pyrrolidone.

7. The preparation according to claim 6, characterized in that The polyvinyl pyrrolidone is one or a combination of povidone K30, povidone K15 and povidone K90.

8. The preparation according to any one of claims 1 to 7, characterized in that The source of the lecithin is one or a combination of soybean lecithin, sunflower lecithin or egg yolk lecithin.

9. The preparation according to any one of claims 1 to 7, characterized in that The content of phosphatidylcholine in phospholipids is 40%-90%.

10. The preparation according to claim 9, characterized in that The content of phosphatidylcholine in phospholipids is 50%-80%.

11. The method for preparing the frankincense extract preparation according to any one of claims 1 to 10, characterized in that: Add frankincense extract and solid dispersion carrier material into an organic solvent, heat and stir; after the reaction is completed, add phospholipids, continue heating and stirring, concentrate and dry, and obtain a product.

12. The preparation method according to claim 11, characterized in that: The organic solvent is one or more combinations of methanol, anhydrous ethanol, acetone and ethyl acetate.

13. The preparation method according to claim 12, characterized in that: The organic solvent is anhydrous ethanol.

14. Use of the frankincense extract preparation according to claims 1-10 and the frankincense extract preparation prepared by the preparation method according to claims 11-13 in the preparation of anti-inflammatory, analgesic, anti-asthmatic, antioxidant, liver disease protection medicines, health foods, dietary supplements and / or foods.