Gastrodia elata and spina date seed oil soft capsule as well as preparation method and application thereof

Abstract

The invention provides a gastrodia elata and spina date seed oil soft capsule and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine extraction and preparation.The preparation method of the gastrodia elata and spina date seed oil soft capsule comprises the following steps that 1, spina date seed coarse powder is pre-extracted with an organic solvent to obtain spina date seed oil and spina date seed residues, and the spina date seed oil is obtained; granulating the spina date seed residues to obtain spina date seed residue particles; 2) extracting the spina date seed residue particles for 2-4 times by using the organic solvent to obtain spina date seed oil and waste residues; 3) mixing the waste residues with gastrodia elata, performing water extraction to obtain a gastrodia elata-spina date seed water extract, and performing concentration and spray drying to obtain a gastrodia elata-spina date seed dry extract; and 4) taking soybean oil and the spina date seed oil as auxiliaries, and taking the gastrodia elata-spina date seed dry extract as a solute to prepare soft capsule contents, thereby obtaining the gastrodia elata-spina date seed oil soft capsule. The gastrodia elata and spina date seed oil soft capsule prepared by the preparation method disclosed by the invention has a remarkable effect of improving sleep.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine extraction and preparation, and particularly relates to a Gastrodia elata and Ziziphus jujuba seed oil soft capsule, a preparation method thereof, and an application thereof. Background Art

[0002] Ziziphus jujuba seed is the seed of the plant Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow of the family Rhamnaceae. Its main effects are: nourishing the liver, calming the mind, soothing the nerves, and arresting sweating. It is used to treat insomnia due to deficiency, palpitation, restlessness, excessive thirst, and night sweats. Ziziphus jujuba seed has a strong sedative and tranquilizing effect, and can regulate sleep and stabilize emotions. Traditional Ziziphus jujuba seed preparations include granules, hard capsules, tablets, extracts, oral liquids, etc. There are few preparations using Ziziphus jujuba seed oil, and the utilization rate of the active ingredients of Ziziphus jujuba seed is not high. However, the raw material price of wild Ziziphus jujuba seed is expensive. If the various active ingredients of Ziziphus jujuba seed cannot be fully utilized, it will cause great waste of Ziziphus jujuba seed resources.

[0003] Gastrodia elata is the dried tuber of the plant Gastrodia elata Bl. of the family Orchidaceae, and has the effects of calming endogenous wind and stopping convulsions, suppressing hyperactive liver-yang, and expelling wind and dredging collaterals. It is mainly used to treat endogenous wind stirring inside, epilepsy and convulsions, dizziness, headache, numbness of limbs, paralysis of hands and feet, rheumatic arthralgia, etc.; Gastrodia elata contains various active ingredients such as gastrodin, parishin, etc., and has a wide range of pharmacological effects. Gastrodia elata combined with various other traditional Chinese medicines has different effects. There are few studies on the pharmacodynamics of the combination of Gastrodia elata and Ziziphus jujuba seed. At present, most of them only stay in the study of the pharmacodynamics of the crude powder of raw Gastrodia elata and Ziziphus jujuba seed, including their preparations. There are no reports or disclosures on the process preparation technology and pharmacodynamics of the extracts of Gastrodia elata and Ziziphus jujuba seed, that is, Ziziphus jujuba seed oil, Ziziphus jujuba seed water extract, Gastrodia elata water extract and their combined preparations. There is no in-depth study on how to combine Ziziphus jujuba seed oil with Gastrodia elata water extract and Ziziphus jujuba seed water extract, and what excipients to use to obtain a drug with a significant biological effect of improving sleep. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a Gastrodia elata and Ziziphus jujuba seed oil soft capsule, a preparation method thereof, and an application thereof.

[0005] The present invention provides a preparation method of a Gastrodia elata and Ziziphus jujuba seed oil soft capsule, comprising the following steps:

[0006] 1) Pre-extracting crude Ziziphus jujuba seed powder with an organic solvent to obtain Ziziphus jujuba seed oil and Ziziphus jujuba seed residue, and granulating the Ziziphus jujuba seed residue to obtain Ziziphus jujuba seed residue granules;

[0007] 2) Extracting the Ziziphus jujuba seed residue granules with the organic solvent for 2 to 4 times to obtain Ziziphus jujuba seed oil and waste residue;

[0008] 3) Mixing the waste residue with Gastrodia elata and extracting with water to obtain a Gastrodia elata-Ziziphus jujuba seed water extract; concentrating and spray-drying to obtain a Gastrodia elata-Ziziphus jujuba seed dry extract;

[0009] 4) Using soybean oil and the wild jujube seed oil as auxiliaries, and using the gastrodia elata-wild jujube seed dry extract as the solute, prepare the soft capsule content, thereby obtaining the gastrodia elata and wild jujube seed oil soft capsule.

[0010] Preferably, the organic solvent used for the pre-extraction in step 1) is n-butane.

[0011] Preferably, the particle size of the wild jujube seed residue particles in step 1) is 5 - 7 mm.

[0012] Preferably, the mass ratio of the waste residue to gastrodia elata in step 3) is (1 - 1.5):1.

[0013] Preferably, the temperature of the water extraction is 42°C - 52°C, the time of the water extraction is 2 - 5 h; the pressure of the water extraction is -0.04 - -0.06 MPa, stirring is accompanied during the water extraction process, and the rotation speed of the stirring is 100 - 150 rpm.

[0014] Preferably, the mass ratio of the soybean oil to the wild jujube seed oil in step 4) is 1:(1 - 3).

[0015] Preferably, the mass ratio of the auxiliary to the solute is (9 - 10):(91 - 90).

[0016] The present invention also provides the gastrodia elata and wild jujube seed oil soft capsule prepared by the described preparation method.

[0017] The present invention also provides the application of the gastrodia elata and wild jujube seed oil soft capsule in the preparation of sleep-aid drugs or health products.

[0018] Compared with the prior art, the present invention has the following beneficial effects: The present invention first uses an organic solvent for lipid-soluble pre-extraction of wild jujube seeds, and then after extrusion and rotary granulation without adding any excipients, extracts wild jujube seeds again, and the oil yield of the fluid extraction is significantly increased by about 5%; then water extraction is carried out on the wild jujube seed residue and gastrodia elata. First, lipid-soluble extraction of wild jujube seed oil is carried out and then water-soluble extraction is carried out, which can maximize the enrichment of two types of active ingredient substances, lipid-soluble and water-soluble, in wild jujube seeds. The gastrodia elata and wild jujube seed oil soft capsule prepared according to the preparation method described in the present invention has a significant sleep-promoting effect. Description of the Drawings

[0019] Figure 1 It is the process flow for the preparation of the gastrodia elata and wild jujube seed oil soft capsule. Detailed Embodiments

[0020] The present invention provides a method for preparing Gastrodia elata and Ziziphus jujuba seed oil soft capsules, comprising the following steps: 1) preliminarily extracting crude Ziziphus jujuba seed powder with an organic solvent to obtain Ziziphus jujuba seed oil and Ziziphus jujuba seed residues, and granulating the Ziziphus jujuba seed residues to obtain Ziziphus jujuba seed residue granules; 2) extracting the Ziziphus jujuba seed residue granules with the organic solvent 2 to 4 times to obtain Ziziphus jujuba seed oil and waste residues; 3) mixing the waste residues with Gastrodia elata, and performing water extraction to obtain a Gastrodia elata-Ziziphus jujuba seed water extract, and concentrating and spray-drying to obtain a Gastrodia elata-Ziziphus jujuba seed dry extract; 4) using soybean oil and the Ziziphus jujuba seed oil as auxiliaries, and using the Gastrodia elata-Ziziphus jujuba seed dry extract as a solute to prepare the soft capsule content, thereby obtaining Gastrodia elata and Ziziphus jujuba seed oil soft capsules.

[0021] In the present invention, crude Ziziphus jujuba seed powder is preliminarily extracted with an organic solvent to obtain Ziziphus jujuba seed oil and Ziziphus jujuba seed residues. In the present invention, it is preferred to crush Ziziphus jujuba seeds to obtain crude Ziziphus jujuba seed powder; the crushing is preferably carried out using an extrusion crushing device provided with a 12 mm stainless steel filter screen. By extruding or rolling Ziziphus jujuba seed granules, the function of crushing Ziziphus jujuba seeds is achieved, and then crude Ziziphus jujuba seed powder is obtained. In the present invention, the organic solvent used for the preliminary extraction is preferably n-butane; in the present invention, the mass-volume ratio of the crude Ziziphus jujuba seed powder to n-butane is 1:(3 - 5); in the present invention, the preliminary extraction is preferably carried out by non-critical extraction, and further preferably, the preliminary extraction pressure is set at 0.5 - 0.8 MPa, the temperature of the preliminary extraction is 35 - 40 °C, and the time of the preliminary extraction is preferably 40 - 50 min.

[0022] In the present invention, the purpose of the preliminary extraction is to first extract a part of the Ziziphus jujuba seed oil in Ziziphus jujuba seeds and reduce the oil content of the Ziziphus jujuba seed material; when the oil content in Ziziphus jujuba seeds is too high, it is not conducive to extracting all the effective components of Ziziphus jujuba seeds.

[0023] After obtaining the Ziziphus jujuba seed residues in the present invention, the Ziziphus jujuba seed residues are granulated to obtain Ziziphus jujuba seed residue granules; in the present invention, the granulation is preferably carried out by extrusion rotary granulation, and the rotation speed is preferably 1000 - 1500 rpm, more preferably 1100 - 1300 rpm, and most preferably 1200 rpm; the present invention further preferably granulates continuously 2 times to obtain Ziziphus jujuba seed granules with a particle size of 5 - 7 mm, preferably 6 mm, meeting the requirements.

[0024] After obtaining the wild jujube seed residue particles, the wild jujube seed residue particles are extracted 2 to 4 times with the organic solvent to obtain wild jujube seed oil and waste residues. In the present invention, the organic solvent is preferably n-butane; the number of extractions is preferably 3 times, and the extraction pressure is 0.5 to 0.8 MPa; the time for each extraction is preferably 30 to 60 minutes, and further preferably, the time for each extraction is gradually decreased. In the specific implementation process of the present invention, the preferred extraction times are 50 minutes, 40 minutes, and 30 minutes respectively. The present invention can extract the active ingredients in wild jujube seeds to the greatest extent through pre-extraction and subsequent 2 to 4 extractions.

[0025] After obtaining the waste residues in the present invention, the waste residues are mixed with gastrodia elata and extracted with water to obtain gastrodia elata-wild jujube seed water extract; in the present invention, the mass ratio of the waste residues to gastrodia elata in the mixture is preferably (1 to 1.5):1, more preferably (1.2 to 1.4):1, and most preferably 1.37:1. In the present invention, the gastrodia elata is preferably gastrodia elata powder, and the gastrodia elata powder is preferably dry gastrodia elata powder, and the dry gastrodia elata powder is preferably obtained by slicing, drying, and pulverizing fresh gastrodia elata; the gastrodia elata powder can also be obtained by mixing fresh gastrodia elata and dry gastrodia elata, and the mass ratio of fresh gastrodia elata to dry gastrodia elata in the mixture is preferably (4 to 6):1, more preferably (4.5 to 5.5):1, and most preferably 5.12:1.

[0026] In the present invention, the temperature for water extraction is preferably 42°C to 52°C, the time for water extraction is preferably 2 to 5 hours, more preferably 2.5 to 4 hours, and most preferably 3 hours; the pressure for water extraction is preferably -0.04 to -0.06 MPa, and stirring is accompanied during the water extraction process, and the rotation speed of the stirring is preferably 100 to 150 rpm, more preferably 110 to 130 rpm. After the water extraction in the present invention is completed, filtration, concentration, drying, and pulverization are preferably carried out to obtain gastrodia elata-wild jujube seed water extract. In the present invention, the filtration preferably passes the supernatant through an 80-mesh filter tank under a water filtration pressure of 0.02 MPa; the concentration is preferably vacuum concentration, the temperature for vacuum concentration is preferably 45 to 55°C, the pressure for vacuum concentration is preferably -0.1 Pa, and the concentration is preferably concentrated to an extract, and the relative density of the extract is preferably 1.1 to 1.2, more preferably 1.12; in the present invention, the drying is preferably spray drying, and after pulverization in the present invention, sieving is preferably carried out, and the mesh number of the sieve is preferably 100 meshes, and the fraction collected under the sieve is the gastrodia elata-wild jujube seed dry extract.

[0027] In the present invention, soybean oil and wild jujube seed oil are used as adjuvants, and the dry extract of gastrodia elata and wild jujube seeds is used as the solute to prepare the soft capsule content, thereby obtaining the gastrodia elata and wild jujube seed oil soft capsule. In the present invention, the mass ratio of the soybean oil to the wild jujube seed oil is 1:(1 - 3), further preferably 1:(1.5 - 2.5), and even more preferably 1:2. In the present invention, the mass ratio of the adjuvant to the solute is preferably (9 - 10):(91 - 90), further preferably (9.2 - 9.8):(90.8 - 90.0), and even more preferably 9.52:90.48. The specification of the gastrodia elata and wild jujube seed oil soft capsule prepared in the present invention is preferably 0.4 - 0.6 g / capsule, further preferably 0.5 g / capsule; the content of the soft capsule is preferably 0.3 - 0.4 g / capsule, further preferably 0.35 g / capsule.

[0028] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0029] Example 1

[0030] 1. Use an extrusion device with a 12 mm stainless steel filter screen to extrude and crush wild jujube seeds to obtain crude wild jujube seed powder.

[0031] 2. Extract wild jujube seed oil

[0032] a) First, pre-extract 48.30 Kg of crude wild jujube seed powder with 193.2 L of n-butane once to extract a part of the wild jujube seed oil; specific conditions: use non-critical extraction, set the pre-extraction pressure at 0.7 MPa, the pre-extraction temperature at 35 °C, and pre-extract for 45 min.

[0033] b) Collect the residue after the first extraction of wild jujube seeds, granulate at 1200 rpm (extrusion rotary granulation), and granulate continuously twice to obtain wild jujube seed granules that meet the requirements (granules with a particle size of 6 mm).

[0034] c) Re-extract the wild jujube seed granules (extract with n-butane, the amount of n-butane is 165.6 L, and the amount of wild jujube seed granules is 41.40 kg), extract three times, and the extraction pressure is 0.7 MPa; according to the time gradient, it is 50 minutes, 40 minutes, and 30 minutes in sequence (after pre-extraction + re-extraction, a total of 4 extractions can extract the active ingredients in wild jujube seeds to the greatest extent), obtain wild jujube seed oil, and at the same time obtain wild jujube seed waste residue.

[0035] 3. Mix the wild jujube seed waste residue and gastrodia elata powder (in a mass ratio of 1.37:1) to obtain a mixed powder;

[0036] Preparation of gastrodia elata powder: Cut fresh gastrodia elata into slices, dry them by air flow to form dry gastrodia elata slices, and then crush the dry gastrodia elata slices into dry gastrodia elata powder.

[0037] Or prepare dried gastrodia elata with the mass ratio of fresh gastrodia elata:dried gastrodia elata = 5.12:1.

[0038] 4. Perform water extraction on the above-mentioned mixed powder, mix it according to the ratio of 90 kg of mixed powder:720 kg of water, and the process parameters are 42°C to 52°C, -0.04 to -0.06 MPa, 120 revolutions per minute.

[0039] 5. Filter the water extract (an 80-mesh filter screen is installed at the bottom of the filter container tank, and filter under the pressure of 0.02 MPa), and concentrate it under reduced pressure to a fluid extract at 45°C to 55°C and under the condition of low pressure -0.1 Pa (the relative density of the extract is 1.12).

[0040] 6. Spray-dry and pulverize the fluid extract (obtain a dried extract of gastrodia elata and wild jujube seed with 100 meshes).

[0041] 7. Manufacture soft capsules.

[0042] Use soybean oil + wild jujube seed oil (mass ratio 1:2) as an adjuvant, use the dried extract of gastrodia elata and wild jujube seed as the solute, and the mass ratio of the adjuvant to the solute is 9.52:90.48; prepare the content of the soft capsule, specification: 0.5 g per capsule, and the content is 0.35 g per capsule.

[0043] The present invention optimizes the method for extracting wild jujube seed oil. The method of pre-extraction, granulating by utilizing the characteristics of the wild jujube seed raw material, and stepwise gradient re-extraction is not disclosed in the prior art. The intuitive advantages brought by the present invention are mild extraction conditions (no need for high temperature and high pressure), short total extraction time, high oil yield, and can extract the effective components in wild jujube seeds to the greatest extent, enabling them to exert various biological effects.

[0044] Charge 48.30 kg of wild jujube seeds, obtain 6.45 kg of wild jujube seed oil after pre-extraction, and the yield is 13.35%. After granulating the residue of wild jujube seeds after the first extraction twice, obtain 41.40 kg of wild jujube seed granules, and perform the second extraction, with a total of 3 re-extractions. After stepwise re-extraction, obtain 5.70 kg of wild jujube seed oil, and the yield is 13.76%. The total amount of wild jujube seed oil obtained from pre-extraction and three re-extractions is 12.15 kg, and the average yield is 25.16%.

[0045] Detect the content of gastrodin in the prepared soft capsules, and entrust the Nanjing Product Quality Supervision and Inspection Institute for detection. Sample quantity: 30 g, sample arrival date: January 21, 2025, inspection date: January 21, 2025 to February 7, 2025.

[0046] Table 1 Detection results

[0047]

[0048] In the present invention, the bioactive substances (aqueous extracts) in Gastrodia elata are combined with the fat-soluble bioactive substances extracted with alcohol and the water-soluble bioactive substances extracted with water in Ziziphus jujuba var. spinosa through reasonable compatibility and assembled in a mixture to extract the active ingredients in Gastrodia elata and Ziziphus jujuba var. spinosa to the greatest extent and enable them to exert biological effects. In the prior art, according to the principle of like dissolves like, the contents of soft capsules are mostly fat-soluble because the shell of soft capsules is fat-soluble. However, there is no report in the prior art on using water-soluble aqueous extracts as the contents of soft capsules. The present invention combines fat-soluble Ziziphus jujuba var. spinosa oil and water-soluble Gastrodia elata and Ziziphus jujuba var. spinosa aqueous extracts to form an emulsion-suspension liquid substance with a homogeneous content of active ingredients and no layering. From the perspective of the proportion of the materials of Ziziphus jujuba var. spinosa oil and Gastrodia elata and Ziziphus jujuba var. spinosa aqueous extracts, the content of this soft capsule is more like an aqueous substance, which is a first in the preparation technology of soft capsules.

[0049] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A method for preparing a soft capsule of Gastrodia elata and jujube seed oil, characterized in that: The following steps are involved: 1) pre-extracting the raw jujube seed powder with an organic solvent to obtain jujube seed oil and jujube seed residue, and granulating the jujube seed residue to obtain jujube seed residue particles; 2) extracting the jujube seed residue particles 2 to 4 times with the organic solvent to obtain jujube seed oil and waste residue; 3) mixing the waste residue with Gastrodia elata, extracting with water to obtain a Gastrodia elata-Semen Suanzaorensis water extract; concentrating and spray drying to obtain a Gastrodia elata-Semen Suanzaorensis dry extract extract; 4) Using soybean oil and the jujube seed oil as adjuvants and the Gastrodia elata-suanziori seed dry extract as a solute to prepare soft capsule contents, thereby obtaining Gastrodia elata-suanziori seed oil soft capsules.

2. The preparation method according to claim 1, characterized in that: The organic solvent used for pre-extraction in step 1) is n-butane.

3. The preparation method according to claim 1, characterized in that: Step 1) The particle size of the jujube seed residue particles is 5 to 7 mm.

4. The preparation method according to claim 1, characterized in that: Step 3) The mass ratio of the waste residue to Gastrodia elata is (1-1.5):

1.

5. The preparation method according to claim 4, characterized in that: The water extraction temperature is 42° C. to 52° C., the water extraction time is 2 to 5 hours, the water extraction pressure is -0.04 to -0.06 MPa, the water extraction process is accompanied by stirring, and the stirring speed is 100 to 150 rpm.

6. The preparation method according to claim 1, characterized in that: The mass ratio of soybean oil to jujube seed oil in step 4) is 1:(1-3).

7. The preparation method according to claim 6, characterized in that: The mass ratio of the auxiliary agent to the solute is (9-10): (91-90).

8. The contents of the Gastrodia elata and jujube seed oil soft capsules obtained by the preparation method according to any one of claims 1 to 7.

9. Use of the Gastrodia elata and jujube seed oil soft capsules according to claim 8 in the preparation of sleep-aiding drugs or health products.

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