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 frankincense extract, the solid dispersion carrier material and cyclodextrin are subjected to one-step reaction according to a specific proportion, so that the operation is simpler, and the reaction efficiency is higher; 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] Patent CN102871848B discloses that pentacyclic triterpenoid compounds can be firstly encapsulated with cyclodextrin and then embedded in liposome vesicles to form cyclodextrin inclusion liposomes. However, it is a two-step reaction, and most of the literatures are sequential reactions, which makes the operation more complicated.

[0004] 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

[0005] 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.

[0006] 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 cyclodextrin, wherein the mass ratio of the frankincense extract to the total mass of the solid dispersion carrier material and the cyclodextrin is 1:1-3, specifically 1:1, 1:1.5, 1:2, 1:2.5, 1:3.

[0007] In some embodiments, the ratio of the mass of frankincense extract to the total mass of the solid dispersion carrier material and cyclodextrin is 1:2.

[0008] In some embodiments, the mass of the solid dispersion carrier material accounts for 15% to 90% of the total mass of the solid dispersion carrier material and the cyclodextrin.

[0009] In some embodiments, the mass of the solid dispersion carrier material accounts for 30% to 75% of the total mass of the solid dispersion carrier material and the cyclodextrin.

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

[0011] In some embodiments, the water-soluble carrier material is a polyvinyl pyrrolidone.

[0012] In some embodiments, polyvinyl pyrrolidones include, but are not limited to, one or a combination of povidone K30, povidone K15, and povidone K90.

[0013] In some embodiments, the cyclodextrin includes, but is not limited to, one or a combination of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin.

[0014] In a second aspect, the present invention provides a method for preparing a frankincense extract preparation, comprising mixing and dissolving the frankincense extract, a carrier material of a solid dispersion and cyclodextrin in an organic solvent, heating and stirring, concentrating and drying to obtain a product.

[0015] In some embodiments, the organic solvent includes, but is not limited to, one or more combinations of methanol, anhydrous ethanol, acetone, and ethyl acetate.

[0016] In some embodiments, the organic solvent is ethanol.

[0017] In some embodiments, the volume ratio of the total mass of the frankincense extract, the carrier material of the solid dispersion and the cyclodextrin to the organic solvent is 1 g: 1-9 mL.

[0018] In some embodiments, the volume ratio of the total mass of frankincense extract, carrier material of solid dispersion and cyclodextrin to the organic solvent is 1g:3-7mL, specifically 1g:3mL, 1g:4mL, 1g:5mL, 1g:6mL, 1g:7mL.

[0019] In some embodiments, the preparation method of the frankincense extract preparation is to dissolve frankincense extract: povidone K30: γ-cyclodextrin in an organic solvent, heat to fully dissolve, stir to react at a certain temperature, and after the reaction is completed, vacuum concentrate and dry to remove anhydrous ethanol to obtain a crude product, and then crush and sieve to obtain the final product.

[0020] In some embodiments, the reaction temperature in the preparation method is 40-80°C, specifically 40°C, 50°C, 60°C, 70°C, 80°C.

[0021] In some embodiments, the reaction time 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.

[0022] 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.

[0023] Beneficial effects:

[0024] The preparation method of the present invention is a one-step reaction, which is superior to a two-step reaction, has simpler operation and higher reaction efficiency; at the same time, the content of the main effective component AKBA in the obtained frankincense extract preparation is greater than 10%, the solubility of AKBA is greater than 35% and can reach up to 75%, and the solubility of KBA can reach up to 100%; and it has good dispersibility in water, and the frankincense extract can be applied to tablets, capsules and other finished dosage forms, thereby expanding the application range of the frankincense extract. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] none DETAILED DESCRIPTION

[0026] 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.

[0027] In the following examples, the total mass of frankincense extract, povidone and cyclodextrin is 30 g.

[0028] Example 1

[0029] The raw materials and auxiliary materials were weighed in a ratio of frankincense extract: povidone K30: γ-cyclodextrin = 1:1:1, dissolved in 150 mL of anhydrous ethanol, and heated until completely dissolved. The mixture was stirred at 60°C for 1 hour. After the reaction, the anhydrous ethanol was removed by vacuum concentration and drying to obtain a crude product. The crude product was crushed and passed through an 80-mesh sieve to obtain the final product, and its solubility was tested. The AKBA content of the obtained product was 11.2%, the solubility of the main active ingredient AKBA was 54.52%, and the solubility of KBA was 98.04%.

[0030] Example 2

[0031] Weigh the raw materials and excipients in a ratio of frankincense extract: povidone K30: β-cyclodextrin = 1:1:1, dissolve in 150mL of anhydrous ethanol, and heat until completely dissolved. Stir the reaction at 60°C for 1 hour. After the reaction is completed, vacuum concentrate and dry to remove anhydrous ethanol to obtain a crude product. The crude product is crushed and sieved through an 80-mesh sieve to obtain the final product, and its solubility is tested. The AKBA content of the obtained product is 11.4%, the solubility of the main active ingredient AKBA is 50.73%, and the solubility of KBA is 87.36%

[0032] Example 3

[0033] The raw materials and auxiliary materials were weighed in a ratio of frankincense extract: povidone K30: α-cyclodextrin = 1:1:1, dissolved in 150 mL of anhydrous ethanol, and heated until completely dissolved. The mixture was stirred at 60°C for 1 hour. After the reaction, the anhydrous ethanol was removed by vacuum concentration and drying to obtain a crude product. The crude product was crushed and passed through an 80-mesh sieve to obtain the final product, and its solubility was tested. The AKBA content of the obtained product was 11.6%, the solubility of the main active ingredient AKBA was 51.37%, and the solubility of KBA was 54.36%.

[0034] Example 4

[0035] The raw materials and auxiliary materials were weighed in a ratio of frankincense extract: povidone K15: γ-cyclodextrin = 1:1:1, dissolved in 150 mL of anhydrous ethanol, and heated until completely dissolved. The reaction was stirred at 60°C for 1 hour. After the reaction was completed, the anhydrous ethanol was removed by vacuum concentration and drying to obtain a crude product. The crude product was crushed and passed through an 80-mesh sieve to obtain the final product, and its solubility was tested. The AKBA content of the obtained product was 11.2%, the solubility of the main active ingredient AKBA was 54.47%, and the solubility of KBA was 100.00%.

[0036] Example 5

[0037] The raw materials and auxiliary materials were weighed in a ratio of frankincense extract: povidone K30: γ-cyclodextrin = 5:3:7, dissolved in 150 mL of anhydrous ethanol, and heated until completely dissolved. The mixture was stirred at 60°C for 1 hour. After the reaction, the anhydrous ethanol was removed by vacuum concentration and drying to obtain a crude product. 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 10.05%, the solubility of the main active ingredient AKBA was 75.03%, and the solubility of KBA was 98.86%.

[0038] Example 6

[0039] The raw materials and auxiliary materials were weighed in a ratio of frankincense extract: povidone K30: γ-cyclodextrin = 2:3:1, dissolved in 150 mL of anhydrous ethanol, and heated until completely dissolved. The reaction was stirred at 60°C for 1 hour. After the reaction was completed, the anhydrous ethanol was removed by vacuum concentration and drying to obtain a crude product. The crude product was crushed and passed through an 80-mesh sieve to obtain the final product, and its solubility was tested. The AKBA content of the obtained product was 10.05%, the solubility of the main active ingredient AKBA was 74.00%, and the solubility of KBA was 96.65%.

[0040] Example 7

[0041] The raw materials and auxiliary materials were weighed in a ratio of frankincense extract: povidone K30: γ-cyclodextrin = 2:1:3, dissolved in 150 mL of anhydrous ethanol, and heated until completely dissolved. The mixture was stirred at 60°C for 1 hour. After the reaction, the anhydrous ethanol was removed by vacuum concentration and drying to obtain a crude product. The crude product was crushed and passed through an 80-mesh sieve to obtain the final product, and its solubility was tested. The AKBA content of the obtained product was 11.00%, the solubility of the main active ingredient AKBA was 27.64%, and the solubility of KBA was 47.71%.

[0042] Comparative Example 1

[0043] Weigh the raw materials and auxiliary materials according to the ratio of frankincense extract: povidone K30 = 1:2, dissolve in 150mL of anhydrous ethanol, and heat until completely dissolved. Stir the reaction at 60°C for 1h. After the reaction is completed, vacuum concentrate and dry to remove anhydrous ethanol to obtain a crude product. The crude product is crushed and sieved through an 80-mesh sieve to obtain the final product, and its solubility is tested. The AKBA content of the obtained product is 11.6%, the solubility of the main active ingredient AKBA is 2.99%, and the solubility of KBA is 14.25%.

[0044] Comparative Example 2

[0045] The raw materials and auxiliary materials were weighed in a ratio of frankincense extract: γ-cyclodextrin = 1:2. The frankincense was dissolved in 150 mL of anhydrous ethanol, and γ-CD was dissolved in 70 mL of water. After complete dissolution, the ethanol phase was slowly added to the water and reacted at 75°C for 2 hours. After the reaction was completed, the anhydrous ethanol was removed by vacuum concentration and drying to obtain a crude product. The crude product was crushed and passed through an 80-mesh sieve to obtain the final product, and its solubility was tested. The AKBA content of the obtained product was 10.6%, the solubility of the main active ingredient AKBA was 14.8%, and the solubility of KBA was 36.01%.

[0046] Comparative Example 3

[0047] 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%.

[0048] Comparative Example 4

[0049] According to the ratio of frankincense extract: povidone K30: γ-cyclodextrin = 1:1:1, add frankincense extract and γ-cyclodextrin according to the formula, add 150mL of anhydrous ethanol, react at 60℃ for 1h, add PVPK30 according to the formula, react at 60℃ for 1h, vacuum concentrate and dry to remove anhydrous ethanol after the reaction, 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 11.4%, the solubility of the main active ingredient AKBA is 14.72%, and the solubility of KBA is 48.23%.

[0050] Comparing the above examples and comparative examples, it is found that in comparative examples 1 and 2, frankincense extract reacts with povidone and cyclodextrin respectively, and the solubility of KBA in the product is only 14.25% and 36.01%, which is far lower than the solubility of KBA in the example product, and the three reactions produce the effect of 1+1>2; comparative examples 3 and 4 are two-step reactions, and the difference lies in the reaction sequence with povidone and cyclodextrin. It can also be found that no matter what the reaction sequence is, the solubility of the two-step reaction product is far lower than the solubility of the product of the one-step reaction in the example. Therefore, the technical effect of the present invention is unexpected.

[0051] The dissolution determination method of AKBA and KBA in the above examples and comparative examples is as follows:

[0052] Dissolution method, specific steps:

[0053] 1. Preheat the dissolution apparatus to 37°C.

[0054] 2. Fill the dissolution apparatus with pH 7.2 PBS buffer and preheat to 37°C.

[0055] 3. Add sample and stir to dissolve (250r / min).

[0056] 4. Take 1h sample.

[0057] 5. Liquid phase detection content.

[0058] 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 cyclodextrin, wherein the mass ratio of the frankincense extract to the total mass of the solid dispersion carrier material and the cyclodextrin 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 cyclodextrin 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 cyclodextrin is 15%-90%.

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 cyclodextrin is 30%-75%.

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 cyclodextrin is one of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin or a combination of several thereof.

9. The method for preparing the frankincense extract preparation according to any one of claims 1 to 8, characterized in that: The frankincense extract, the carrier material of the solid dispersion and cyclodextrin are mixed and dissolved in an organic solvent, heated and stirred, concentrated and dried to obtain a product.

10. The preparation method according to claim 9, characterized in that: The organic solvent is one or more combinations of methanol, anhydrous ethanol, acetone and ethyl acetate.

11. The preparation method according to claim 10, characterized in that: The organic solvent is anhydrous ethanol.

12. Use of the frankincense extract preparation according to claims 1-8 and the frankincense extract preparation prepared by the preparation method according to claims 9-11 in the preparation of anti-inflammatory, analgesic, anti-asthmatic, antioxidant, liver disease protection medicines, health foods, dietary supplements and / or foods.