Plant essential oil microemulsion for external use for relieving thyroid nodules and preparation method thereof

Abstract

The application discloses a plant essential oil microemulsion for relieving thyroid nodules and a preparation method thereof. The microemulsion comprises an aqueous phase extract, an essential oil composition and PEG-40 hydrogenated castor oil, the aqueous phase extract is prepared from radix scrophulariae, preknowing son and lamiophlomis, the essential oil composition comprises bergamot essential oil, frankincense essential oil, helichrysum essential oil, pelargonium essential oil, lavender essential oil, spigelia anthemia essential oil, bisabolol and vitamin E acetate. In the preparation, an oil phase and a solubilizing agent are combined to form a solubilizing system, and then the solubilizing system is combined with the aqueous phase extract to form the microemulsion. The microemulsion has uniform particle size, good stability, high transdermal absorption rate, refreshing skin feeling and pleasant aroma, can form nerve-endocrine-local circulation regulation, can effectively relieve the compression and discomfort caused by the thyroid nodules on the neck, and is mild and non-irritating to the skin.

Description

Technical Field

[0001] This invention belongs to the technical field of essential oil care products, specifically relating to a plant essential oil microemulsion for external use to relieve thyroid nodules and its preparation method. Background Technology

[0002] Thyroid nodules are a common endocrine disorder in clinical practice. In Traditional Chinese Medicine (TCM), they are classified as "goiter," with the core pathogenesis being emotional distress and liver qi stagnation leading to qi stagnation, phlegm accumulation, and blood stasis in the neck. With the fast pace of modern life and increased work pressure, the detection rate of thyroid nodules is rising annually. Patients often experience discomfort such as neck fullness, pressure, and anxiety. Currently, besides regular observation and surgery, interventions for benign nodules are limited, and oral medications have certain side effects. Patients often seek topical care products to help alleviate symptoms. Plant essential oils, due to their advantages of rapid transdermal absorption and diverse active ingredients, have been explored for neck care. However, existing essential oil products often use compound oils or ordinary creams directly, resulting in poor stability, low transdermal absorption, high skin irritation, and limited efficacy, leading to unsatisfactory relief for thyroid nodules.

[0003] Therefore, there is an important practical need to develop a safe, stable, transdermal-absorbable plant essential oil preparation that can effectively relieve discomfort from cervical thyroid nodules. Summary of the Invention

[0004] The purpose of this invention is to provide a plant essential oil microemulsion for external use to relieve thyroid nodules and its preparation method, aiming to solve at least one technical problem in the background art.

[0005] The objective of this invention is achieved as follows: To better implement this research project, this invention provides a topical plant essential oil microemulsion for relieving thyroid nodules, comprising an aqueous extract, an essential oil composition, and PEG-40 hydrogenated castor oil; the aqueous extract comprises aqueous extracts of Scrophularia ningpoensis, Gynostemma pentaphyllum, and Lycopus lucidus; the essential oil composition comprises bergamot essential oil, frankincense essential oil, immortelle essential oil, geranium essential oil, lavender essential oil, vetiver essential oil, bisabolol, and vitamin E acetate.

[0006] Preferably, in the aqueous extract, the weight ratio of Scrophularia, Asarum heterotropoides and Lycopus lucidus is (2~4):(1.5~3):(1~2); based on the total weight of the plant essential oil microemulsion as 1000 parts by weight, the equivalent raw medicinal material of the aqueous extract is: Scrophularia 60~100g, Asarum heterotropoides 40~80g, and Lycopus lucidus 30~50g.

[0007] Preferably, the total weight of the plant essential oil microemulsion is 1000 parts by weight, and the essential oil composition contains the following components in parts by weight: 20-40 parts bergamot essential oil; 10-20 parts frankincense essential oil; 3-8 parts immortelle essential oil; 5-12 parts geranium essential oil; 3-8 parts lavender essential oil; 1-5 parts vetiver essential oil; 1-3 parts bisabolol; and 0.5-2 parts vitamin E acetate.

[0008] Preferably, the weight ratio of the PEG-40 hydrogenated castor oil to the essential oil composition is (2.2~2.8):1.

[0009] Preferably, the plant essential oil microemulsion further comprises excipients: 3-8 parts of 1,2-pentanediol, 0.5-1.5 parts of water-soluble lauryl acetone, 3-8 parts of glycerin, 0.5-1.2 parts of phenoxyethanol compound preservative, and the remainder of purified water.

[0010] Preferably, the plant essential oil microemulsion has a pH value of 5.5 to 6.5 and an osmotic pressure of 280 to 320 mOsmol / kg.

[0011] This invention also provides a method for preparing the plant essential oil microemulsion, comprising the following steps: S1: Preparation of aqueous extract - Take Scrophularia ningpoensis, Gynostemma pentaphyllum and Lycopus lucidus, decoct with water to extract, filter, concentrate, add ethanol to make the alcohol content reach 60%~80%, let stand for 6~24 hours for alcohol precipitation, filter to remove precipitate, recover ethanol to obtain aqueous extract. S2: Oil phase premixing - Bisabolol and vitamin E acetate are mixed with vetiver essential oil and heated and stirred at 30~45℃ until the vetiver is completely diluted and dissolved. Then, immortelle essential oil, frankincense essential oil, bergamot essential oil, geranium essential oil and lavender essential oil are added and stirred until well mixed to obtain the mixed oil phase. S3: Solubilization Premixing – Mix PEG-40 hydrogenated castor oil with 1,2-pentanediol, add the mixed oil phase obtained in step S2, and stir until a clear and transparent solubilization system is formed; S4: Microemulsion formation—Under stirring conditions, the aqueous extract obtained in step S1 is rapidly added to the solubilization system obtained in step S3, and homogenized until a clear and transparent or pale blue opalescent microemulsion is formed; the homogenization speed is preferably 3000~5000 rpm, and the homogenization time is 10~30 minutes; S5: Post-processing—Add glycerin, water-soluble lauryl acetone and preservative, add purified water, adjust pH value, filter using a 0.45μm microporous membrane, and fill to obtain the final product. Compared with the prior art, the present invention has the following beneficial effects:

[0012] This invention utilizes a combination of specific plant water extracts and essential oils in a microemulsion carrier to produce a significant synergistic effect. Scrophularia softens and disperses nodules, Anemarrhena soothes the liver and regulates qi, and Lycopus lucidus invigorates blood and removes blood stasis. The combination of these three herbs intervenes in nodule formation through multiple pathways: regulating qi, invigorating blood, and dispersing nodules. Bergamot essential oil soothes the liver and relieves depression (lowers cortisol), frankincense essential oil regulates qi and invigorates blood, disperses nodules, immortelle essential oil removes blood stasis, geranium essential oil balances endocrine function (regulates hormone levels), lavender essential oil calms the nerves, vetiver essential oil soothes and calms, and bisabolol has anti-inflammatory and soothing effects. These eight oil-phase active ingredients, along with the three herbal water extracts, form a triple regulatory loop of "neuro-endocrine-local circulation." The microemulsion system significantly reduces the irritation of essential oils and improves transdermal absorption, allowing the active ingredients to effectively penetrate the subcutaneous tissue of the neck, relieving swelling and discomfort caused by thyroid nodules.

[0013] The plant essential oil microemulsion of this invention has a particle size of 20-60 nm, is thermodynamically stable, and does not separate during long-term storage. Its 24-hour cumulative drug penetration rate through isolated rat skin is more than twice that of conventional mixed oils. Animal experiments show that it can significantly reduce the nodule volume and decrease thyroid tissue proliferation indicators in goiter model rats. After 4 weeks of human trials, most subjects experienced softening of neck nodules, shortening of the long axis as shown by ultrasound, and no skin irritation. The composition of this invention is safe, stable, easy to prepare, and has good application prospects. Detailed Implementation

[0014] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0015] This invention provides a plant essential oil microemulsion for external use to relieve thyroid nodules, comprising an aqueous extract, an essential oil composition, and PEG-40 hydrogenated castor oil; the aqueous extract comprises aqueous extracts of Scrophularia ningpoensis, Gynostemma pentaphyllum, and Lycopus lucidus; the essential oil composition comprises bergamot essential oil, frankincense essential oil, immortelle essential oil, geranium essential oil, lavender essential oil, vetiver essential oil, bisabolol, and vitamin E acetate.

[0016] Specifically, in the aqueous extract, the weight ratio of Scrophularia, Asarum heterotropoides and Lycopus lucidus is (2~4):(1.5~3):(1~2); based on the total weight of the plant essential oil microemulsion as 1000 parts by weight, the equivalent raw medicinal material in the aqueous extract is: Scrophularia 60~100g, Asarum heterotropoides 40~80g, and Lycopus lucidus 30~50g.

[0017] Specifically, the total weight of the plant essential oil microemulsion is 1000 parts by weight, and the essential oil composition contains the following components in parts by weight: 20-40 parts of bergamot essential oil; 10-20 parts of frankincense essential oil; 3-8 parts of immortelle essential oil; 5-12 parts of geranium essential oil; 3-8 parts of lavender essential oil; 1-5 parts of vetiver essential oil; 1-3 parts of bisabolol; and 0.5-2 parts of vitamin E acetate.

[0018] Specifically, the weight ratio of the PEG-40 hydrogenated castor oil to the essential oil composition is (2.2~2.8):1.

[0019] Specifically, the plant essential oil microemulsion also contains excipients: 3-8 parts of 1,2-pentanediol, 0.5-1.5 parts of water-soluble lauryl acetone, 3-8 parts of glycerin, 0.5-1.2 parts of phenoxyethanol compound preservative, and the remainder of purified water.

[0020] Specifically, the plant essential oil microemulsion has a pH value of 5.5~6.5 and an osmotic pressure of 280~320 mOsmol / kg.

[0021] This invention also provides a method for preparing the plant essential oil microemulsion, comprising the following steps: S1: Preparation of aqueous extract - Take Scrophularia ningpoensis, Gynostemma pentaphyllum and Lycopus lucidus, decoct with water to extract, filter, concentrate, add ethanol to make the alcohol content reach 60%~80%, let stand for 6~24 hours for alcohol precipitation, filter to remove precipitate, recover ethanol to obtain aqueous extract. S2: Oil phase premixing - Bisabolol and vitamin E acetate are mixed with vetiver essential oil and heated and stirred at 30~45℃ until the vetiver is completely diluted and dissolved. Then, immortelle essential oil, frankincense essential oil, bergamot essential oil, geranium essential oil and lavender essential oil are added and stirred until well mixed to obtain the mixed oil phase. S3: Solubilization Premixing – Mix PEG-40 hydrogenated castor oil with 1,2-pentanediol, add the mixed oil phase obtained in step S2, and stir until a clear and transparent solubilization system is formed; S4: Microemulsion formation—Under stirring conditions, the aqueous extract obtained in step S1 is rapidly added to the solubilization system obtained in step S3, and homogenized until a clear and transparent or pale blue opalescent microemulsion is formed; the homogenization speed is preferably 3000~5000 rpm, and the homogenization time is 10~30 minutes; S5: Post-processing—Add glycerin, water-soluble lauryl acetone and preservative, add purified water, adjust pH value, filter using a 0.45μm microporous membrane, and fill to obtain the final product. Example 1

[0022] A plant essential oil microemulsion for relieving thyroid nodules, with the following components per 1000g: Aqueous extract: Extracts corresponding to 80g of Scrophularia ningpoensis, 60g of Gynostemma pentaphyllum, and 40g of Lycopus lucidus (Preparation: Boil the three herbs twice with water, 1 hour each time, combine the decoctions, filter, concentrate to about 500mL, add 95% ethanol to 70% alcohol content, refrigerate and stand for 12 hours, filter, recover ethanol from the filtrate and concentrate to obtain about 180g of aqueous extract).

[0023] Essential oil composition: 30g bergamot essential oil, 15g frankincense essential oil, 5g immortelle essential oil, 8g geranium essential oil, 5g lavender essential oil, 3g vetiver essential oil, 2g bisabolol, 1g vitamin E acetate.

[0024] PEG-40 hydrogenated castor oil: 172.5g (total oil phase weight 69g, ratio 2.5:1).

[0025] Excipients: 5g 1,2-pentanediol, 1g water-soluble lauryl acetone, 5g glycerin, 0.8g phenoxyethanol compound preservative, and purified water to make up to 1000g.

[0026] Preparation method: S1: Prepare approximately 180g of aqueous extract according to the above method for aqueous extraction, and set aside for later use.

[0027] S2: Mix 2g of bisabolol, 1g of vitamin E acetate and 3g of vetiver essential oil, heat to 40℃ and stir until completely dissolved, then add immortelle essential oil, frankincense essential oil, bergamot essential oil, geranium essential oil and lavender essential oil in sequence, stir evenly to obtain a mixed oil phase.

[0028] S3: Mix 172.5g of PEG-40 hydrogenated castor oil with 5g of 1,2-pentanediol, add to the mixed oil phase, and stir at 300rpm until a clear and transparent solubilized system is formed.

[0029] S4: Under homogenization stirring at 4000 rpm, the aqueous extract is quickly added to the solubilization system, and homogenization is continued for 15 minutes to form a transparent microemulsion with a light blue opalescent sheen.

[0030] S5: Add 5g of glycerol, 1g of water-soluble lauryl acetone, and 0.8g of phenoxyethanol compound preservative. Add purified water to a total weight of 1000g, stir well, adjust the pH to 6.2 with 0.1mol / L citrate-sodium citrate buffer, filter through a 0.45μm microporous membrane, and fill into containers.

[0031] The resulting microemulsion had a pH of 6.2, an osmotic pressure of 305 mOsmol / kg, an average particle size of 38 nm (dynamic light scattering method), and an appearance of a pale yellow, clear, transparent liquid with a pale blue opalescence. Example 2

[0032] Component dosage: Aqueous extract corresponding to 60g of Scrophularia ningpoensis, 40g of Lycopus lucidus, and 30g of Lycopus lucidus; Essential oil composition: 20g of bergamot oil, 10g of frankincense oil, 3g of immortelle oil, 5g of geranium oil, 3g of lavender oil, 1g of vetiver oil, 1g of bisabolol, and 0.5g of vitamin E acetate; PEG-40 hydrogenated castor oil to oil phase weight ratio 2.2:1 (95.7g); 3g of 1,2-pentanediol, 0.5g of water-soluble lauryl acetone, 3g of glycerin, 0.5g of preservative, and purified water to 1000g. Preparation method was the same as in Example 1, homogenization speed 3000rpm, time 30 minutes, pH adjusted to 5.5. The average particle size of the obtained microemulsion was 52nm. Example 3

[0033] Component dosage: Aqueous extract corresponding to 100g of Scrophularia ningpoensis, 80g of Lycopus lucidus, and 50g of Lycopus lucidus; Essential oil composition: 40g of bergamot oil, 20g of frankincense oil, 8g of immortelle oil, 12g of geranium oil, 8g of lavender oil, 5g of vetiver oil, 3g of bisabolol, and 2g of vitamin E acetate; PEG-40 hydrogenated castor oil to oil phase weight ratio 2.8:1 (274.4g); 8g of 1,2-pentanediol, 1.5g of water-soluble lauryl acetone, 8g of glycerin, 1.2g of preservative, and purified water to 1000g. Preparation method was the same as in Example 1, homogenization speed 5000rpm for 10 minutes, pH adjusted to 6.5. The average particle size of the obtained microemulsion was 24nm.

[0034] Comparative Example 1 (no microemulsion formed) The components were the same as in Example 1, but the PEG-40 hydrogenated castor oil was replaced with an equal amount of water. After the same stirring operation, the resulting product was emulsified and quickly separated into layers, failing to form a clear microemulsion.

[0035] Comparative Example 2 (lacking aqueous extract) The aqueous extract in Example 1 was replaced with an equal volume of purified water, while the remaining components and preparation were the same, resulting in a transparent microemulsion.

[0036] Comparative Example 3 (lacking the prophet and Zellan) The aqueous extract was extracted solely from 120g of Scrophularia ningpoensis (equivalent to the total amount of raw herb), and the rest was the same as in Example 1. Experiment Example 1: Stability Test

[0037] The microemulsion from Example 1 was placed at 40°C and -5°C for 30 days, and centrifuged at 3000 rpm for 30 minutes, respectively. The appearance and particle size were observed. The results showed that under all conditions, the sample remained clear and transparent or had a pale blue opalescence, without stratification or precipitation, and the particle size variation was less than 10%, indicating excellent stability. In contrast, Comparative Example 1, without preparation, had already stratified. Experiment Example 2: Transdermal Permeability Experiment

[0038] Using a Franz diffusion cell and isolated abdominal skin of SD rats as a model, the supply chamber was filled with microemulsions from Example 1, Comparative Example 2, and a physically mixed oil (excluding aqueous extract and solubilizing system) containing the same essential oil combination. The receiving solution was pH 7.4 phosphate buffer (containing 20% ​​PEG400). Samples were taken at 2, 4, 6, 8, and 24 hours to detect the cumulative permeation of bergamot lactone (a marker). Results showed that the cumulative permeation at 24 hours was 2.4 times that of the physically mixed oil in Example 1 and 1.7 times that of Comparative Example 2. This indicates that the microemulsion of the present invention significantly improved the transdermal absorption of the active ingredient, and the presence of the aqueous extract further promoted penetration. Experiment Example 3: Effects on a rat model of goiter

[0039] SD rats were induced to develop thyroid enlargement by drinking 0.1% propylthiouracil for 14 days. They were divided into three groups: model group, Example 1 group (neck skin was cut and applied once daily for 14 consecutive days), Comparative Example 2 group, and Comparative Example 3 group. After the administration period, the rats were sacrificed, and the thyroid glands were harvested, weighed, and the thyroid index was calculated. Histological morphology was observed by HE staining. Results showed that compared with the model group, the thyroid index in Example 1 group was significantly reduced (P<0.01), follicular epithelial proliferation was decreased, and colloid accumulation was reduced. Comparative Example 2 and Comparative Example 3 groups showed some effect, but the effect was weaker than that of Example 1. This indicates that the aqueous extract and essential oil composition of this invention has a synergistic inhibitory effect on thyroid enlargement and nodular lesions. Experiment Example 4: Human Trial Effects

[0040] With the approval of the ethics committee, 30 patients with benign thyroid nodules diagnosed by ultrasound (maximum nodule length 0.5–2.0 cm) were recruited. The microemulsion of Example 1 was applied to the affected area of ​​the neck twice daily, morning and evening, for 4 consecutive weeks. The length of the same nodule was measured by ultrasound before and after the trial, and subjective pressure scores (0–10 points) were recorded. Results showed that after 4 weeks, the average length of the nodules decreased by (0.23 ± 0.12) cm, and the pressure score decreased from (4.5 ± 1.2) to (1.8 ± 0.9). 85% of the subjects experienced a softening sensation to the touch. No skin redness, swelling, itching, or other irritation reactions occurred in any of the subjects. Experimental Example 5: Skin Irritation Test

[0041] Healthy rabbits were used for self-comparison between their left and right sides. The left side was coated with the microemulsion of Example 1, and the right side was coated with physiological saline. The application was repeated for 7 days, and the skin reaction was observed. The results showed that no erythema or edema was observed on the skin of the side of Example 1, and the score was 0, indicating no skin irritation.

[0042] The above results indicate that the plant essential oil microemulsion of the present invention has uniform particle size, good stability, high transdermal absorption efficiency, refreshing feel, and pleasant aroma. Through the synergistic effect of multiple components, it forms a neuro-endocrine-local circulation regulation, which can effectively relieve the pressure and discomfort caused by thyroid nodules in the neck, and is gentle and non-irritating to the skin and safe to use.

[0043] The above description is merely a preferred embodiment of the present invention and does not limit the scope of the patent. Any equivalent structural transformations made based on the inventive concept of the present invention and the content of this specification, or direct / indirect applications in other related technical fields, are included within the scope of patent protection of the present invention.

Claims

1. A plant essential oil microemulsion for external use to relieve thyroid nodules, characterized in that, It contains an aqueous extract, an essential oil composition, and PEG-40 hydrogenated castor oil; The aqueous extract contains aqueous extracts of Scrophularia, Gynostemma pentaphyllum, and Lycopus lucidus. The essential oil composition comprises bergamot oil, frankincense oil, immortelle oil, geranium oil, lavender oil, vetiver oil, bisabolol, and vitamin E acetate.

2. The plant essential oil microemulsion according to claim 1, characterized in that, In the aqueous extract, the weight ratio of Scrophularia, Asarum heterotropoides and Lycopus lucidus is (2~4): (1.5~3): (1~2). Based on the total weight of the plant essential oil microemulsion as 1000 parts by weight, the equivalent raw medicinal material in the aqueous extract is: Scrophularia 60~100g, Asarum heterotropoides 40~80g, and Lycopus lucidus 30~50g.

3. The plant essential oil microemulsion according to claim 1, characterized in that, Based on a total weight of 1000 parts by weight of the plant essential oil microemulsion, the essential oil composition comprises the following components in parts by weight: Bergamot essential oil 20-40 parts; 10-20 parts frankincense essential oil; 3-8 parts immortelle essential oil; 5-12 parts geranium essential oil; 3-8 parts lavender essential oil; 1-5 parts vetiver essential oil; 1-3 parts of bisabolol; Vitamin E acetate 0.5 to 2 parts.

4. The plant essential oil microemulsion according to claim 1, characterized in that, The weight ratio of the PEG-40 hydrogenated castor oil to the essential oil composition is (2.2~2.8):

1.

5. The plant essential oil microemulsion according to claim 1, characterized in that, Based on a total weight of 1000 parts by weight of the plant essential oil microemulsion, it also contains the following excipients: 3-8 parts of 1,2-pentanediol; 0.5-1.5 parts of water-soluble lauryl acetone; 3-8 parts glycerin; A phenoxyethanol compound preservative is prepared in 0.5 to 1.2 parts. The remaining amount of purified water.

6. The plant essential oil microemulsion according to claim 1, characterized in that, The plant essential oil microemulsion has a pH of 5.5-6.5 and an osmotic pressure of 280-320 mOsmol / kg.

7. A method for preparing a plant essential oil microemulsion according to any one of claims 1-6, characterized in that, Includes the following steps: S1: Preparation of aqueous extract - Take Scrophularia ningpoensis, Gynostemma pentaphyllum and Lycopus lucidus, decoct with water to extract, filter, concentrate, add ethanol to make the alcohol content reach 60%~80%, let stand for 6~24 hours for alcohol precipitation, filter to remove precipitate, recover ethanol to obtain aqueous extract. S2: Oil phase premixing - Bisabolol and vitamin E acetate are mixed with vetiver essential oil and heated and stirred at 30~45℃ until the vetiver is completely diluted and dissolved. Then, immortelle essential oil, frankincense essential oil, bergamot essential oil, geranium essential oil and lavender essential oil are added and stirred until well mixed to obtain the mixed oil phase. S3: Solubilization Premixing – Mix PEG-40 hydrogenated castor oil with 1,2-pentanediol, add the mixed oil phase obtained in step S2, and stir until a clear and transparent solubilization system is formed; S4: Microemulsion formation—Under stirring conditions, the aqueous extract obtained in step S1 is rapidly added to the solubilization system obtained in step S3, and homogenized until a clear and transparent or pale blue opalescent microemulsion is formed. S5: Post-processing—Add glycerin, water-soluble lauryl acetone and preservative, add purified water, adjust pH, filter, and fill to obtain the final product.

8. The preparation method according to claim 7, characterized in that, In step S4, the homogenization speed is 3000~5000 rpm and the homogenization time is 10~30 minutes.

9. The preparation method according to claim 7, characterized in that, In step S5, a 0.45μm microporous membrane is used for filtration, and the pH is adjusted to 6.0~6.5.