CN1931232B - Oil-in-water nanometer perilla seed oil emulsion oral liquid and its preparation process - Google Patents

Abstract

The invention discloses an oil-in-water perilla seed oil nanoemulsion oral liquid. The nanoemulsion oral liquid is prepared from surfactant, oil, perilla seed oil and distilled water according to the following method: weighing according to the formula Surfactant, used alone or compounded with co-surfactant, calculate HLB value, select oil according to its HLB value, adjust its ratio, so that the HLB value required for emulsification is similar to the HLB of the surfactant phase; according to the law Change the ratio of the surfactant phase to the oil phase, add perilla seed oil in the formula ratio, stir well, slowly add distilled water at 20°C to 25°C and stir thoroughly until a clear, transparent, low viscosity and fluid yellow color is formed Or colorless and transparent O/W nanoemulsion. The invention improves the drug stability of the perilla seed oil in the processing process, improves the bioavailability, delays the drug metabolism time in the body, reduces the consumption of auxiliary materials, reduces the production cost, and has broad market prospects in the field of medicine.

Description

A kind of oil-in-water perilla seed oil nanoemulsion oral liquid and preparation method thereof

technical field

The invention belongs to the fields of medicine, food and health products, and relates to a medicine preparation and a preparation method thereof, in particular to a transparent and stable oil-in-water perilla seed oil nanoemulsion oral liquid and a preparation method thereof. the

Background technique

Perilla was first recorded in the earliest medical classic "Shen Nong's Herbal Classic" in the Han Dynasty in my country 2,500 years ago. The book says: "Su Zi tastes sweet and warm, long-term consumption can lighten the body", and it also says: "Su is comfortable and has the power of promoting qi and blood, so it is called Su." Its taste is pungent in nature, and it has the effects of lowering qi and eliminating illness, relieving asthma, and moistening the intestines. It has been recorded in Chinese Pharmacopoeia, but its clinical application only stays at the level of decocting perilla seed in water, lowering Qi and eliminating illness, relieving asthma and moistening intestines. So far, no matter clinical or folk, perilla has not been further developed and researched. the

Modern medical research has found that perilla seeds do not contain cholesterol, but are rich in α-linolenic acid, with a content of 51% to 70%. α-linolenic acid is an essential fatty acid for the human body. It has a variety of physiological regulation functions on the human body. It can lower blood pressure, lower blood lipids, resist arteriosclerosis, prevent cardiovascular diseases, enhance memory, prevent Alzheimer's disease, promote mental development, and improve IQ. In 1993, the Food and Agriculture Organization of the United Nations and the World Health Organization jointly issued a statement: In view of the importance of α-linolenic acid and the general lack of human beings, it was decided to promote α-linolenic acid worldwide. In 1990, the laws of the United States, France, Japan and other countries must add α-linolenic acid to designated foods, while the per capita intake of α-linolenic acid in my country is less than half of the recommended amount by the World Health Organization. However, perilla seed oil has poor solubility, unstable physical properties, is volatile, easy to rancid, difficult to preserve, difficult to disperse in water, and low utilization rate. the

Contents of the invention

For the problems and defects of the above-mentioned prior art, the object of the present invention is to provide a kind of even and accurate content, stable quality, and easy to prepare perilla seed oil nanoemulsion oral liquid. the

The technical scheme that realizes the above-mentioned invention object is oil-in-water type perilla seed oil nanoemulsion oral liquid, and it is made up of the raw material of following weight ratio:

Surfactant 21.19%～45.00%

Oil 4.03%～10.00%

Perilla seed oil 0.10%～15.00%

Distilled water 50%～72.00%

In the selection of surfactants, the present invention selects non-ionic surfactants with good non-toxicity and biocompatibility. Non-ionic surfactants are relatively stable in solution, not easily affected by strong electrolytes, inorganic salts, and acid-base, and have good compatibility with other surfactants, and have less hemolysis. Theoretically, the preparation of O/W nanoemulsion requires the HLB value of the surfactant to be between 8 and 18. Considering the simplicity of the preparation process, that is, the ease of forming the nanoemulsion and the stability of the prepared nanoemulsion In the present invention, a liquid nonionic surfactant with HLB between 10 and 15 is selected, or compounded with a nonionic surfactant with HLB<10. The optional surfactants are: one or more of castor oil polyoxyethylene ether (such as EL-40), hydrogenated castor oil polyoxyethylene ether (such as RH-40), Tween-80 and Span-80 kind of mixture. the

The present invention is based on the principle that when the HLB of the surfactant required for the emulsified oil phase is similar to the surfactant, the formed emulsion is stable. The oils selected include liquid paraffin, vitamin E oil, wheat germ oil, almond oil, and acetic acid One or more mixtures of ethyl esters and olive oil. These oils are liquid at room temperature and have no bad smell. the

Another object of the present invention is to provide the preparation method of oil-in-water perilla seed oil nanoemulsion oral liquid, the steps are as follows:

(1) Preparation of surfactant phase Weigh the surfactant according to the proportion of the formula, use it alone or compound it with co-surfactant in proportion, calculate the HLB value of the system, and stir well. The HLB values of common emulsifiers can be found in some chemical handbooks, such as "Chemical Product Handbook" published by Chemical Press. Since the hydrophilic-lipophilic balance (HLB) value of the surfactant is additive, the HLB value of the surfactant can be obtained by the mass average method. For example, after two surfactants A and B are mixed, the hydrophilic-lipophilic equilibrium HLBAB value of the mixed surfactant is

HLBAB＝(WAHLBA+WBHLBB)/(WA+WB) 

In the formula, WA, WB——the quality of mixture surfactant A, B;

HLBA, HLBB - HLB values of surfactants A and B. the

(2) Preparation of the oil phase According to the HLB value of the surfactant phase, select one or several oils and adjust their ratio so that the HLB value required for emulsification is similar to the HLB of the surfactant phase. the

(3) Change the ratio of the surfactant phase and the oil phase according to the rule of 9:1 to 1:9, add perilla seed oil in the formula ratio therein, stir fully, slowly add distilled water at 20°C to 25°C and stir fully, Until a clear, transparent, low viscosity and fluid yellow or colorless O/W nanoemulsion is formed. the

The invention is detected by a transmission electron microscope, the droplet diameter is distributed between 10-100nm, the appearance is yellow or colorless transparent liquid, and has good stability:

1. Stability over time

Stability over time refers to the extent to which the appearance of the nanoemulsion oral liquid changes over time when it is stored under natural room temperature conditions. The perilla seed oil nanoemulsion oral liquid is persistently transparent, and no turbidity or precipitation is found, which shows that it has good stability over time. This is an important indicator for evaluating nanoemulsion oral liquid. the

2. Heat storage stability

The perilla seed oil nanoemulsion oral liquid was placed in a test tube, sealed, and stored in a constant temperature water bath at 37°C for 14 days. The liquid appeared transparent after thermal storage. the

3. Freezing stability

The perilla seed oil nanoemulsion oral liquid was stored in the refrigerator at -4°C for one week. Return to room temperature. If the nanoemulsion oral solution becomes solid at -4°C, returns to room temperature, returns to transparent, and remains transparent after one week, it is considered that the freezing resistance is good. the

4. Acceleration stability

The perilla seed oil nanoemulsion oral solution was placed in a test tube, sealed, and centrifuged at a speed of 15,000 r/min for 20 minutes. There was no stratification, and it was still clear and transparent. the

The oil-in-water type perilla seed oil nanoemulsion oral liquid of the present invention has various effects such as lowering blood pressure, lowering blood fat, resisting arteriosclerosis, preventing cardiovascular disease, enhancing memory, preventing senile dementia, promoting intellectual development, and improving IQ. . Clinically, it can be used for the treatment of hyperlipidemia, hypertension, atherosclerosis, senile dementia, bronchial asthma and other diseases. Usage: Oral, 0.3g per day. the

Compared with the prior art, the oil-in-water perilla oil nanoemulsion oral liquid has the following advantages:

1) High thermodynamic stability. The operation is relatively simple during preparation, no phase separation, no precipitation, and the storage stability is improved;

2) Good light transmission, any inhomogeneity or the existence of sediment can be easily found, and the sensory quality is improved;

3) The anti-corrosion performance is improved, because the dispersed phase liquid is relatively small, which can prevent the invasion of bacteria and increase the solubility of some active ingredients;

4) It has a good solubilization effect, which can effectively improve the solubility of insoluble drugs;

5) It can improve the solubility of perilla seed oil and delay the disappearance time of perilla seed oil, thereby improving the bioavailability of perilla seed oil;

6) The method has simple process and is suitable for large-scale production. the

Detailed ways

The beneficial effect of the medicine of the present invention will be further elaborated below through pharmacodynamic tests and comparative tests. the

Test Example 1 Comparative test of perilla seed oil nanoemulsion oral liquid for lowering blood fat and other preparations

Select 9 Wistar rats with basically the same age and body weight, and feed them with a high-fat diet made of 3% cholesterol, 10% lard, 0.2% methylthiouracil, and 86.8% basal feed for 20 days to establish a high-fat model. Divided into 3 groups on average, the first group was treated with Qianlin Perilla Oil Soft Capsules (each containing 8 mg perilla oil) produced by Shantou Baorui Pharmaceutical Co., Ltd. with the batch number _TY3483, and each rat took 2 times a day , 1 capsule each time, with the aid of a gag, the capsules were fed to rats. The second group was treated with Dongyu Xuepingkang produced by Shenyang Dongyu Xinboer Technology Co., Ltd. (2000) No. 0698. Each rat took 3 capsules once a day, crushed and fed in the feed. Hello. The third group is treated with perilla seed oil nanoemulsion oral liquid of the present invention, and each rat is oral 0.3g (containing perilla seed oil 15mg) every day, and after 3 weeks, the serum triglyceride (TG) of each group of rats is measured. ), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ratio of LDL-C to high-density lipoprotein cholesterol (HDL-C) (LDL-C/HDL-C), and atherosclerotic Increased value of the index (Al). As a result, it was found that the above indicators of the three groups of rats were all reduced to varying degrees, especially the third group was the most obvious. It shows that perilla seed oil nanoemulsion oral liquid is more effective in lowering blood lipid than Qianlin perilla oil soft capsule and Dongyu Xuepingkang, and the dose is lower. the

Test Example 2 Comparative test of perilla seed oil nanoemulsion oral hypolipidemic efficacy and other preparations

Choose 12 young rats with essential hypertension (SHR-SP), half male and half male, and divide them into three groups on average according to quantity and sex. The first group is given perilla seed oil nanoemulsion oral liquid 10% oil 15mg) mixed material feeding, the second group was fed with 6% safflower oil (containing safflower oil 15mg) mixed material produced by Shanghai Diyuan Food Co., Ltd., and the third group was fed with Shantou Baorui Pharmaceutical Co., Ltd. The batch number is _TY3483 Qianlin perilla oil soft capsules (each containing 8mg perilla oil), each take 2 times a day, 1 capsule each time, the result is that the male rats in the first group are more than the male rats in the second and third groups. The average survival time of the rats was prolonged by 17%, 15%, and the average survival time of the female rats was 40%, 32% longer than that of the male rats; the diastolic pressure of the first group was 10% lower (2.8kPa) on average than the second and third groups; The brain examination results of the dead mice showed that the main cause of death was cerebral hemorrhage. It fully shows that the efficacy of perilla seed oil nanoemulsion oral liquid is higher than that of safflower oil and Qianlin perilla oil soft capsule. the

The preparation method of perilla seed oil nanoemulsion oral liquid of the present invention is further described by the examples given by the inventor below. the

Example 1

Use the oil selected by calculating the HLB value, surfactant, and co-surfactant to draw a pseudo-ternary phase diagram according to the rule of 9:1 to 1:9 to determine the optimal ratio. Accurately weigh 1.8g of Tween-80, 0.6g of Span-80, and 0.6g of liquid paraffin, put them into a beaker, and mix them thoroughly by manual stirring at room temperature of 25°C, then add 0.1g of perilla seed oil directly, Stir well, then slowly add distilled water to it, and manually stir while adding distilled water. At the beginning, the system viscosity is small. As the amount of distilled water increases, the system will become viscous. At this time, the system may appear liquid crystal or water-in-oil nanometer. Milk, continue to add dropwise and constantly stir, when the system suddenly becomes thinner, what produce now is the stable yellow transparent oil-in-water type perilla seed oil nanoemulsion oral liquid, claiming that its total weight is 10.0g. the

Example 2

Use the oil selected by calculating the HLB value, surfactant, and co-surfactant to draw a pseudo-ternary phase diagram according to the rule of 9:1 to 1:9 to determine the optimal ratio. Accurately weigh 3.6g of polyoxyethylene hydrogenated castor oil, 0.4g of wheat germ oil, and 0.05g of vitamin E oil, put them into a beaker, and mix them thoroughly by manual stirring at room temperature of 24°C. Add it directly, stir until it is completely dissolved, then slowly add distilled water to it, and manually stir while adding distilled water. Water-in-oil type nanoemulsion, continue to drop and constantly stir, when the system suddenly becomes thinner, what produce this moment is the stable colorless transparent oil-in-water type perilla seed oil nanoemulsion oral liquid, and its total weight is called 10.35g. the

Example 3

Use the oil selected by calculating the HLB value, surfactant, and co-surfactant to draw a pseudo-ternary phase diagram according to the rule of 9:1 to 1:9 to determine the optimal ratio. Accurately weigh 4.5g of polyoxyethylene hydrogenated castor oil and 0.5g of olive oil, put them into a beaker, and mix them thoroughly by manual stirring at room temperature of 25°C, add 1.0g of perilla seed oil directly, and stir until completely dissolved , then slowly add distilled water to it, and stir manually while adding distilled water. At the beginning, the system viscosity is small. As the amount of distilled water increases, the system will become viscous. At this time, the system may appear liquid crystal or water-in-oil nanoemulsion. Continue to add dropwise and constantly stir, when the system becomes thinner suddenly, what produces now is the stable colorless transparent oil-in-water type perilla seed oil nanoemulsion oral liquid, claiming that its total weight is 10.0g. the

Example 4

Use the oil selected by calculating the HLB value, surfactant, and co-surfactant to draw a pseudo-ternary phase diagram according to the rule of 9:1 to 1:9 to determine the optimal ratio. Accurately weigh 4.0g of polyoxyethylene hydrogenated castor oil and 1.0g of almond oil, put them into a beaker, and mix them thoroughly by manual stirring at room temperature of 20°C, add 1.5g of perilla oil directly, and stir until completely dissolved , then slowly add distilled water to it, and stir manually while adding distilled water. At the beginning, the system viscosity is small. As the amount of distilled water increases, the system will become viscous. At this time, the system may appear liquid crystal or water-in-oil nanoemulsion. Continue to add dropwise and constantly stir, when the system becomes thinner suddenly, what produces now is the stable colorless transparent oil-in-water type perilla seed oil nanoemulsion oral liquid, claiming that its total weight is 10.0g. the

Example 5

Use the oil selected by calculating the HLB value, surfactant, and co-surfactant to draw a pseudo-ternary phase diagram according to the rule of 9:1 to 1:9 to determine the optimal ratio. Accurately weigh 1.40g of Tween-80, 0.70g of Span-80, and 0.90g of liquid paraffin, put them into a beaker, and mix them thoroughly by manual stirring at room temperature of 22°C, add 0.01g of perilla seed oil directly, Stir well, then slowly add distilled water to it, and manually stir while adding distilled water. At the beginning, the system viscosity is small. As the amount of distilled water increases, the system will become viscous. At this time, the system may appear liquid crystal or water-in-oil nanometer. Milk, continue to drop and constantly stir, when the system suddenly becomes thinner, what produce now is the stable yellow transparent oil-in-water type perilla seed oil nanoemulsion oral liquid, claiming that its total weight is 9.91g. the

Example 6

Use the oil selected by calculating the HLB value, surfactant, and co-surfactant to draw a pseudo-ternary phase diagram according to the rule of 9:1 to 1:9 to determine the optimal ratio. Accurately weigh 4.5g of polyoxyethylene castor oil, 0.5g of ethyl acetate, and 0.03g of vitamin E oil, put them into a beaker, and mix them thoroughly by manual stirring at room temperature of 24°C, and directly add 0.07g of perilla seed oil Add, stir thoroughly, then slowly add distilled water to it, and manually stir while adding distilled water. At the beginning, the system viscosity is small. As the amount of distilled water increases, the system will become viscous. At this time, the system may appear liquid crystal or water-in-oil Type nanoemulsion, continue to drop and constantly stir, when system suddenly becomes thinner, what produce this moment is stable colorless transparent oil-in-water type perilla seed oil nanoemulsion oral liquid, claims its weight as 11.1g. the

Example 7

Use the oil selected by calculating the HLB value, surfactant, and co-surfactant to draw a pseudo-ternary phase diagram according to the rule of 9:1 to 1:9 to determine the optimal ratio. Accurately weigh 3.6g of polyoxyethylene hydrogenated castor oil, 0.4g of ethyl acetate, and 0.02g of vitamin E oil, put them into a beaker, and mix them thoroughly by manual stirring at room temperature of 23°C, and mix 0.8g of perilla seed oil Add directly, stir thoroughly, then slowly add distilled water, and manually stir while adding distilled water. At the beginning, the viscosity of the system is small. As the amount of distilled water increases, the system will become viscous. At this time, the system may appear liquid crystal or oily. Water-in-water nanoemulsion, continue to drop and stir continuously, when the system suddenly becomes thinner, what is produced at this time is a stable colorless and transparent oil-in-water perilla seed oil nanoemulsion oral liquid, which weighs 10.42g . the

Claims (2)

1. an oil-in-water type perilla seed oil nanoemulsion oral liquid, is characterized in that it is made up of the raw material of following weight ratio: surfactant 21.19%～45.00%, oil 4.03%～10.00%, perilla Seed oil 0.10%～15.00% and distilled water 50%～72.00%; The surfactant is any one or a mixture of castor oil polyoxyethylene ether, hydrogenated castor oil polyoxyethylene ether, Tween-80 and Span-80; The oil is any one or a mixture of liquid paraffin, vitamin E oil, almond oil, wheat germ oil, ethyl acetate and olive oil. 2. The perilla seed oil nanoemulsion oral liquid according to claim 1, characterized in that: the particle size of the perilla seed oil nanoemulsion oral liquid is 10nm-100nm.