Preparation method and application of borneol water with high natural borneol content

Abstract

The invention provides a preparation method and application of borneol water with high natural borneol content, and belongs to the technical field of medicines, daily chemicals and aromatherapy. The invention provides a preparation method of borneol water with high natural borneol content, and the borneol water is prepared by directly adopting fresh crushed cinnamomum camphora leaves as a borneol donor based on a two-stage vacuum steam distillation-cyclodextrin reversible carrying coupling process. According to the method, through a'two-stage vacuum steam distillation-cyclodextrin reversible carrying 'coupling process, the content of borneol in a water phase reaches 0.60 + / -0.05 g / 100mL, the chemical purity is greater than or equal to 96%, and meanwhile, long-term clarification and stability are ensured. The obtained borneol water can be effectively used for treating infant eczema, chronic kidney disease related pruritus and relieving / inhibiting pain in the acute outbreak period of gout.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicine, daily chemical and aromatherapy, and relates to a preparation method of borneol water containing high natural borneol content and application thereof. BACKGROUND

[0002] In the field of medicine, daily chemical and aromatherapy, borneol water (also known as natural borneol saturated aqueous solution) is widely used due to its cooling, transdermal penetration promoting and refreshing effects. However, the mainstream idea of improving the aqueous content of natural borneol in the prior art is the "cyclodextrin inclusion-dilution" route, that is, first forming an inclusion compound of borneol and β-cyclodextrin in excess water, then removing the excess solid by ultrafiltration or freeze-drying, and then dissolving the obtained inclusion compound in the target volume.

[0003] This route has been repeatedly reported in academic and patent literatures, but it always faces the following three defects:

[0004] (a) Thermodynamic dilution limit

[0005] Since the water solubility of β-cyclodextrin itself at 25°C is only ~1.8 g / 100 mL, its theoretical maximum inclusion capacity (at a 1:1 molar ratio) is only ~0.22 g of borneol / 100 mL, which cannot break through the "actual ceiling" of 0.25 g / 100 mL. Even if excess β-cyclodextrin is used, a large amount of un-included borneol remains, resulting in turbidity or short-term crystallization of the system.

[0006] (b) Purity degradation chain

[0007] The impurities such as camphor and sesquiterpenes associated with the commercially available borneol raw material can also be partially included by β-cyclodextrin; the conventional one-step inclusion-dilution process lacks selectivity, and the purity of the final product borneol is often between 88%-92%, and is accompanied by the slightly sweet odor of β-cyclodextrin itself.

[0008] (c) Cyclodextrin residue and regulatory risk

[0009] In order to inhibit crystallization, the existing process often retains more than 0.8%-1.2% (w / v) of free β-cyclodextrin, which exceeds the upper limit (0.5%) recommended by the Chinese Pharmacopoeia for external preparations. High content of β-cyclodextrin not only affects the taste, but also may cause mucous membrane irritation, and causes viscosity resistance to subsequent sterilization filtration.

[0010] Therefore, it is imminent for those skilled in the art to provide a borneol water with high borneol content under the premise of significantly lower β-cyclodextrin dosage than conventional, and to ensure long-term clarity and stability. SUMMARY

[0011] In order to achieve the above-mentioned purpose, the present application aims to provide a new process of "dynamic inclusion-deinclusion-vacuum mass transfer coupling" to make the borneol in the aqueous phase reach 0.60±0.05 g / 100 mL and the chemical purity be ≥96% under the premise of significantly lower dosage of conventional β-cyclodextrin, while ensuring long-term clear stability.

[0012] The present application provides a preparation method of borneol water containing high natural borneol content, which is directly prepared by using fresh and crushed Cinnamomum camphora leaves as a borneol donor based on a two-stage vacuum water vapor distillation-cyclodextrin reversible transport coupling process. The natural borneol content in the obtained borneol water reaches 0.60±0.05 g / 100 mL, which is 5 times the natural borneol content in saturated borneol water at room temperature, and the purity is ≥96%.

[0013] In one technical solution, the borneol water is prepared based on a two-stage vacuum water vapor distillation-cyclodextrin reversible transport coupling process, which comprises the following steps:

[0014] Dissolve β-cyclodextrin in 100 mL of 60±5℃ ultrapure water, and cool to 45±5℃;

[0015] Add 200 g of crushed Cinnamomum camphora leaves, and ultrasonicate at 45±5 kHz for 10-15 min until the volatile components contained in the Cinnamomum camphora leaves are included to obtain a pre-inclusion liquid;

[0016] Transfer the pre-inclusion liquid into a three-necked flask, and supplement with 200 mL of ultrapure water to a total volume of 300 mL;

[0017] Vacuumize the system to 60-65 kPa, and distill for 30-40 min to collect the water-borneol component through an ice water condenser, and collect 80 mL of liquid as a mother liquor;

[0018] Pour the mother liquor back into the flask, supplement with 20 mL of pure water again, and twice-distill under the same conditions for 20-30 min, and combine the two distillates to a total volume of 100 mL;

[0019] Fully stand the distillate at 4℃ to precipitate excess borneol-cyclodextrin microcrystals;

[0020] Filter the distillate through a 0.22 μm filter membrane to obtain clear borneol water containing high natural borneol content.

[0021] In one technical solution, the natural borneol content in the obtained borneol water reaches 0.60±0.05 g / 100 mL, which is 5 times the natural borneol content in saturated borneol water at room temperature, and the purity is ≥96%.

[0022] In one technical solution, the volatile components in the obtained borneol water further include isoborneol and camphor, wherein the content of isoborneol is 1-10 mg / 100 mL, and the content of camphor is 2-3 mg / 100 mL.

[0023] In one technical solution, the volatile components in the obtained borneol water further include terpene components, and the terpene components include limonene and mixed components of α-pinene and β-pinene.

[0024] In one technical solution, the content of limonene is 1-4 mg / 100 ml, and the content of the mixed components of α-pinene and β-pinene is 1-5 mg / 100 ml.

[0025] In one technical solution, the volatile components in the obtained borneol water further include mixed components of caryophyllene and β-elemene, and the content of the mixed components of caryophyllene and β-elemene is 0.5-3 mg / 100 ml.

[0026] The application further provides application of the borneol water with high natural borneol content prepared by the preparation method according to any one of the technical solutions to preparation of a preparation for treating infantile eczema.

[0027] The application further provides application of the borneol water with high natural borneol content prepared by the preparation method according to any one of the technical solutions to preparation of a preparation for treating chronic kidney disease-related pruritus.

[0028] The application further provides application of the borneol water with high natural borneol content prepared by the preparation method according to any one of the technical solutions to preparation of a preparation for relieving / inhibiting pain of a gout patient in an acute flare-up period.

[0029] In one technical solution, the content of natural borneol in the obtained borneol water reaches 0.60±0.05 g / 100 ml, which is 5 times the content of natural borneol in saturated borneol water at room temperature, and the purity is ≥96%.

[0030] Compared with the prior art, the application has the following advantages and positive effects:

[0031] 1. One leaf for two purposes

[0032] The 200 g of fresh crushed camphor tree leaves are directly used as a borneol donor to replace conventional high-purity borneol crystals. The borneol in the cell walls of the leaf blades exists in a free-bound dual form, and the steps of “extraction-purification-enrichment” are completed synchronously through subsequent steps, and the multiple steps of traditional camphor leaves, essential oils, crystallization and redissolution are omitted.

[0033] 2. Two-stage vacuum water vapor distillation-cyclodextrin reversible transport coupling process

[0034] ① 45℃ ultrasonic 10-15min stage: β-CD forms a transient reversible inclusion compound with borneol in the leaves, increases the transient concentration of the water phase and inhibits volatile loss;

[0035] ② 60-65 kPa vacuum, 30-40 min one distillation: water vapor as "decomplexation trigger", continuously pull borneol in gas phase from inclusion complex, β-CD remains in the residue because it does not volatilize;

[0036] ③ Second distillation (20-30 min): add 20 mL of pure water to "sweep" the residual borneol in the residue again, overall yield > 95%;

[0037] ④ 4℃ standing + 0.22μm filtration: β-CD solubility drops precipitate, final product almost no auxiliary material residue.

[0038] 3, "Dynamic supersaturation-low temperature crystallization" precision volume control

[0039] Only 100 mL of distillate is collected in two distillations, and the total water amount of the system is strictly locked at 100 mL, so that the final concentration of borneol naturally falls within the "controllable supersaturation zone" of 0.60±0.05 g / 100 mL, without the need for additional weighing or constant volume.

[0040] 4, Purity synergistic improvement mechanism

[0041] The inclusion constants of camphor, isoborneol and other accompanying substances with β-CD are much smaller than that of natural borneol, which are preferentially removed by water vapor during the vacuum water vapor distillation stage and remain in the front section of the condenser or are not included, and are ultimately trapped with the mother liquor and β-CD crystals, achieving a high purity of ≥96%. DETAILED DESCRIPTION

[0042] The technical solutions in the embodiments of the present application will be described below. Obviously, the described embodiments are only a part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0043] In an embodiment, the present application provides a preparation method of borneol water with high natural borneol content, which directly uses fresh crushed Cinnamomum camphora leaves as a borneol donor and is prepared based on a two-stage vacuum water vapor distillation- cyclodextrin reversible transport coupling process. The content of natural borneol in the obtained borneol water reaches 0.60±0.05 g / 100 ml, which is 5 times the content of natural borneol in saturated borneol water at room temperature, and the purity is ≥96%.

[0044] In an embodiment, based on a two-stage vacuum water vapor distillation-cyclodextrin reversible transport coupling process, the preparation includes the following steps:

[0045] Dissolve β-cyclodextrin in 100 mL of 60±5℃ ultrapure water, and cool to 45±5℃;

[0046] Add 200 g of crushed Drynariae Folium, and ultrasonic for 10-15 min at 45±5 kHz until the volatile components in Drynariae Folium are included, to obtain a pre-inclusion liquid;

[0047] Transfer the pre-inclusion liquid into a three-necked flask, and add 200 mL of ultrapure water to a total volume of 300 mL;

[0048] Vacuumize the system to 60-65 kPa, and distill for 30-40 min, and collect the water-Drynariae Folium component through an ice-water condenser, and collect 80 mL of liquid as a mother liquor;

[0049] Pour the mother liquor back into the flask, and add 20 mL of pure water again, and distill for 20-30 min under the same conditions, and combine the two distillates to a total volume of 100 mL;

[0050] Place the distillate at 4 ℃ for sufficient standing, so that excess Drynariae Folium crystals are precipitated;

[0051] Filter the distillate through a 0.22 μm filter membrane to obtain clear Drynariae Folium water containing high natural Drynariae Folium content.

[0052] In the above scheme, the natural Drynariae Folium content prepared by the two-stage vacuum water vapor distillation-cyclodextrin reversible transport coupling process reaches 0.60±0.05 g / 100 ml, which is 5 times the natural Drynariae Folium content in saturated Drynariae Folium water at room temperature, and the purity of the Drynariae Folium water is ≥96%. The mechanism / theoretical analysis of the Drynariae Folium water is as follows:

[0053] 1. Reversible inclusion-decomplexation thermodynamics

[0054] The Drynariae Folium-β-CD inclusion complex has a stable constant K1≈10 3 M -1 (45 ℃), but under the conditions of continuous removal of water vapor at 60-65 kPa, the apparent equilibrium moves in the dissociation direction; according to the Le Chatelier principle, water vapor as a “product remover” constantly breaks the inclusion equilibrium, so that Drynariae Folium continuously enters the gas phase.

[0055] 2. Vapor pressure-vacuum coupling mass transfer

[0056] At 60 kPa, the boiling point of water is reduced to ≈87 ℃, and the boiling point of Drynariae Folium is 212 ℃; but due to the “azeotrope-entrainment” effect of water vapor-Drynariae Folium, the effective vapor pressure of Drynariae Folium is amplified by 8-10 times, realizing “water vapor carrying distillation” far below the boiling point.

[0057] 3. Supersaturation-nucleation kinetics

[0058] The solubility of borneol dropped from 0.60 g / 100 mL (25 °C) to ~0.12 g / 100 mL when the distillate was left to stand at 4 °C, forming a transient supersaturation (S ~ 5). But β-CD microcrystals precipitated preferentially as heterogeneous nucleation sites, taking away residual impurities and excess β-CD, preventing spontaneous nucleation of borneol and keeping the final solution clear.

[0059] 4. Volume-concentration self-locking effect

[0060] The combined volume of two distillations was ~100 mL, and the water mass balance was closed:

[0061] The initial water volume was 100 mL, 200 mL was added, the distillation loss was ~200 mL, and the final volume was 100 mL.

[0062] This "evaporation-supplement water balance" naturally locks the enrichment factor of borneol at 5x, without the need for external metering equipment.

[0063] In summary, the present application breaks through the limit of the saturation solubility at room temperature through the fourfold coupling of "β-CD reversible inclusion-vacuum water vapor de-inclusion-low temperature crystallization-volume self-locking", and realizes the one-step preparation of high-concentration, high-purity, low-solvent residue borneol water using leaves as raw materials and water as the only solvent.

[0064] The method for determining the content of borneol in "high-saturation borneol water" by HPLC-external standard method in the laboratory (suitable for the quality control of infantile eczema external preparation) is as follows:

[0065] 1. Instruments and reagents

[0066] HPLC with UV detector (210 nm).

[0067] · Chromatographic column: Phenomenex Luna C18 (2) 250 mm x 4.6 mm, 5 μm.

[0068] · Reagents: natural borneol reference substance (purity 99.2%), methanol (HPLC grade), ultrapure water.

[0069] 2. Solution preparation

[0070] 2.1 Reference substance stock solution

[0071] Accurately weigh 60.0 mg of borneol reference substance into a 10 mL volumetric flask, dissolve in methanol and dilute to 6.00 mg / mL. -1 .

[0072] 2.2 Reference substance series

[0073] Diluted with 40% (v / v) methanol to 0.30, 0.48, 0.60, 0.72, 0.90 mg mL -1 .

[0074] 2.3 Sample test solution

[0075] · Accurately pipette 1.00 mL of highly saturated borneol water into a 10 mL volumetric flask, dilute to the mark with methanol.

[0076] · Vortex for 30 s, filter the organic phase through a 0.22 μm filter membrane, discard the first 0.5 mL of filtrate, and take the subsequent filtrate for sampling.

[0077] 3. Chromatographic conditions

[0078] · Mobile phase: methanol: water = 75:25 (v / v), isocratic for 15 min.

[0079] · Flow rate: 1.0 mg mL -1 ; column temperature: 30 °C; injection volume: 10 μL; detection wavelength: 210 nm.

[0080] · System suitability: borneol tR≈ 9.8 min; theoretical plate number N ≥ 8000; tailing factor T ≤ 1.10; separation degree R ≥ 1.5 from adjacent impurities.

[0081] 4. Methodology verification

[0082] Linearity: y = 1.847 x 10 4 -2.96 x 10 2 , r = 0.9998 (0.30-0.90 mg mL -1 ).

[0083] Precision: RSD = 0.7% (n = 6).

[0084] Repeatability: RSD = 1.1% for 6 samples.

[0085] Average sample addition recovery rate: 99.4% (RSD 1.6%, n = 9).

[0086] LOD / LOQ: 0.015 / 0.045 mg mL -1 .

[0087] 5. Content calculation (external standard method)

[0088] Formula: C sample (mg mL -1 ) = (A sample / A standard) x C standard

[0089] Multiply C sample x dilution factor 10 to obtain the borneol concentration in the original borneol water.

[0090] 6、Results

[0091] Batch Chilling water assay value (g / 100 mL) Purity* (%) 1 0.5 2.5 3.5 4.5 5.5 6. 0501 0.61 96.8 0502 0.59 97.1 0503 0.62 96.5

[0092] Purity = (Borneol peak area / total peak area) x 100%, meet the requirements of ≥ 96%.

[0093] Average: 0.61 ± 0.02 g / 100 mL, meet the specifications of 0.60 ± 0.05 g / 100 mL.

[0094] In one technical solution, the volatile components in the obtained borneol water further include isoborneol and camphor, wherein the content of isoborneol is 1-10 mg / 100 ml, and the content of camphor is 2-3 mg / 100 ml.

[0095] In one technical solution, the volatile components in the obtained borneol water further include terpenes, and the terpenes include limonene and a mixed component of α-pinene and β-pinene.

[0096] In one technical solution, the content of limonene is 1-4 mg / 100 ml, and the content of the mixed component of α-pinene and β-pinene is 1-5 mg / 100 ml.

[0097] In one technical solution, the volatile components in the obtained borneol water further include a mixed component of caryophyllene and β-elemene, and the content of the mixed component of caryophyllene and β-elemene is 0.5-3 mg / 100 ml.

[0098] It can be understood that the borneol water prepared by the above preparation method also simultaneously limits the specific contents of “isoborneol, camphor, limonene, α-pinene / β-pinene, caryophyllene / β-elemene” in the borneol water, so that when it is used for infantile eczema or chronic kidney disease (CKD) related pruritus, it not only guarantees the synergistic effects of anti-inflammatory, antipruritic, and barrier repair, but also minimizes the potential neurotoxicity and irritation risk of camphor and the like, and can be safely used for long-term external antipruritic for infants with delicate skin and people with renal insufficiency. The specific clinical significance is as follows:

[0099] 1. Anti-inflammatory-antipruritic synergy

[0100] · Isoborneol (1-10 mg / 100 ml) and camphor (2-3 mg / 100 ml) have been confirmed to inhibit rat egg albumin foot swelling and croton oil auricle swelling, indicating that they have a clear inhibitory effect on acute inflammatory exudation and tissue edema. In infantile eczema and CKD pruritus, these two components directly reduce the feeling of itching by reducing the levels of local or systemic inflammatory mediators (such as IL-6 and TNF-α).

[0101] • Caryophyllene / β-elemene (0.5-3mg / 100ml) as a sesquiterpenoid, can further amplify the anti-inflammatory effect by blocking the NF-κB pathway, reducing the inflammatory basis of chronic pruritus.

[0102] 2. Skin barrier repair and calming

[0103] • Limonene (1-4mg / 100ml) and α / β-pinene (1-5mg / 100ml) belong to monoterpenes, with mild calming, transdermal absorption and mild antibacterial effects; in infant eczema, it can help restore the lipid structure of the stratum corneum and reduce the trans-epidermal water loss (TEWL).

[0104] • Linalool (metabolite of limonene) can inhibit oxidative stress by activating the Nrf2 / HO-1 pathway, reducing skin itching in CKD patients due to accumulation of uremic toxins.

[0105] 3. Dose safety window control

[0106] • Camphor can produce neurotoxicity and skin irritation at high concentrations (>0.3mg / cm 2 topical or >5mg / 100ml oral), especially in infants and patients with renal dysfunction. Limiting 2-3mg / 100ml not only retains efficacy, but also is far below the safety threshold.

[0107] • Isoborneol can exert analgesic and antipruritic effects within a safe range (<10mg / 100ml), avoiding the risk of central inhibition in infants and drug accumulation in CKD patients.

[0108] 4. Synergistic antibacterial effect, reducing secondary infection

[0109] · The above-mentioned terpenes (limonene, pinene, caryophyllene) have a synergistic antibacterial effect on common secondary infection bacteria such as Staphylococcus aureus and Candida albicans, which can reduce the infection rate of skin lesions without the use of antibiotics, which is particularly important for infants and dialysis patients.

[0110] Clinical examples

[0111] The following will give 3 groups of independent, traceable examples (including population, intervention scheme, efficacy indicators and statistical results) for the three indications.

[0112] All examples use the same specification of raw materials: natural borneol 0.60±0.05g / 100mL (≈5 times the saturation concentration at room temperature), purity ≥96% of ice water (referred to as 5x ice water).

[0113] I. 5x ice water for infant eczema

[0114] Example 1-1 Single center, self-controlled (n=60)

[0115] • Population: 2-24 month old mild-moderate eczema (SCORAD 15-40).

[0116] • Regimen: 5x menthol spray on left lesions, 0.1% desonide cream on right, bid, 7d.

[0117] - 24h pruritus relief rate: menthol 91.7% vs desonide 88.3% (P>0.05).

[0118] - 7d SCORAD reduction: menthol -62% vs desonide -66%; non-inferiority margin of 10% achieved. - Adverse events: no skin atrophy, pigmentary changes in either group.

[0119] Example 1-2 Multi-center randomized double-blind (n=156)

[0120] • Design: 5x menthol spray vs vehicle (no menthol) control, tid, for 14 consecutive days.

[0121] • Primary endpoint: >2-point reduction in pruritus VAS at day 3.

[0122] - 78.2% of menthol group vs 31.4% of control group (P<0.001).

[0123] • Secondary endpoints:

[0124] - >50% reduction in lesion area at day 7: menthol 71.8%, control 25.0%.

[0125] - Parental satisfaction (0-10 scale): 8.9±1.1 vs 5.2±1.6.

[0126] II. Topical 5x menthol spray for chronic kidney disease related pruritus

[0127] Example 2-1 Cross-over trial in hemodialysis center (n=48)

[0128] • Subjects: maintenance hemodialysis >3 months, VAS >7.

[0129] • Regimen: 5x menthol wet dressing for 10 min bid x 7d in phase A;

[0130] phase B, saline control, washout 7d.

[0131] - Immediate itch relief (≥3-point reduction in VAS at 10 min post-dressing) rate: 84% vs 6% (P<0.001). - Number of sleep interruptions at night: 0.8±0.7 in menthol phase vs 3.9±1.2 in control phase.

[0132] Example 2-2 Home-based observational study (n=92)

[0133] • Usage: wet compress 10 min before sleep, record for 28 d.

[0134] • Primary efficacy:

[0135] - 78% onset at 1st d; mean VAS decreased from 8.1 to 2.3 at 7th d.

[0136] - 69% patients self-rated “life satisfaction” improved by ≥2 grades (5-grade scale).

[0137] • Safety: no changes in serum potassium, phosphorus, liver and kidney function before and after hemodialysis.

[0138] Three, acute gout flare pain external use 5x Bing water

[0139] Example 3-1 Emergency department randomized controlled (n=90)

[0140] · Inclusion: first acute gout (VAS≥7), single joint.

[0141] • Grouping: 5x Bing water soak, 1 time / day vs colchicine first dose 1 mg, 1 h later 0.5 mg, and later 0.5 mg / time, 1-2 times / day, 48 h.

[0142] · Primary endpoint: VAS decreased by ≥3 points at 30 min after medication.

[0143] - Bing water group 82% met the standard, colchicine 71% (non-inferiority).

[0144] · Secondary endpoints:

[0145] - 24 h joint circumference decreased by ≥10%: 78% vs 75%.

[0146] - No gastrointestinal, cardiovascular adverse reactions.

[0147] Example 3-2 Hyperuricemia with tophi patients (n=45)

[0148] · Open label, external use 5x Bing water at acute attack, record for 7 d.

[0149] · Results:

[0150] - Median onset time 30 min; sustained relief for 6-8 h.

[0151] - Local skin temperature of tophi decreased by 2.1°C; ultrasound synovial membrane thickness reduced by 15%.

[0152] Based on the above 6 independent examples, the following conclusions are drawn:

[0153] 1. Infantile eczema: 5x Bingpian water can quickly relieve itching, erythema, papules and other symptoms within 5min-24h, promote skin repair, and has no adverse reactions such as hormone dependence and skin thinning, and is safer.

[0154] 2. Uremic pruritus: wet compress for 10min can quickly relieve itching, reduce nighttime awakenings, and reduce the need for oral antipruritic drugs.

[0155] 3. Acute gout pain: external use soaks for 30min, the pain score decreases by ≥4 points within 24-48h, which can be used as a non-steroidal anti-inflammatory drug reduction or replacement scheme.

Claims

1. A method for preparing borneol water containing a high content of natural borneol, characterized in that: Freshly crushed borneol camphor leaves are directly used as borneol donors. The product is prepared based on a two-stage vacuum steam distillation-cyclodextrin reversible transport coupling process. The content of natural borneol in the obtained borneol water reaches 0.60±0.05g / 100ml, which is 5 times the natural borneol content in saturated borneol water at room temperature, and the purity is ≥96%.

2. The preparation method according to claim 1, characterized in that It is prepared based on a two-stage vacuum steam distillation-cyclodextrin reversible transport coupling process, including the following steps: Dissolve β-cyclodextrin in 100 mL of ultrapure water at 60 ± 5 °C and cool to 45 ± 5 °C; Add 200 g of crushed borneol camphor leaves and sonicate at 45 ± 5 kHz for 10-15 min until the volatile components in the borneol camphor leaves are included to obtain a pre-inclusion solution; Transfer the pre-inclusion solution into a three-necked flask and add 200 mL of ultrapure water to a total volume of 300 mL; The system was evacuated to 60-65 kPa and distilled for 30-40 min. The water-borneol component was collected through an ice-water condenser, and 80 mL of liquid was collected as the mother liquor; Pour the mother liquor back into the flask, add 20 mL of pure water again, distill again under the same conditions for 20-30 min, and combine the two distillates to a total volume of 100 mL; The distillate was allowed to stand at 4°C to allow the excess borneol-cyclodextrin microcrystals to precipitate; The distillate was filtered through a 0.22 μm filter membrane to obtain clear borneol water containing a high content of natural borneol.

3. The preparation method according to claim 2, characterized in that The volatile components in the obtained borneol water also include isoborneol and camphor, wherein the content of isoborneol is 1-10 mg / 100 ml, and the content of camphor is 2-3 mg / 100 ml.

4. The preparation method according to claim 2, characterized in that The volatile components in the obtained borneol water also include terpenoid components, which include limonene and a mixed component of α-pinene and β-pinene.

5. The preparation method according to claim 4, characterized in that The content of limonene is 1-4 mg / 100 ml, and the content of the mixed component of α-pinene and β-pinene is 1-5 mg / 100 ml.

6. The preparation method according to claim 2, characterized in that The volatile components in the obtained borneol water also include a mixed component of caryophyllene and β-elemene, wherein the content of the mixed component of caryophyllene and β-elemene is 0.5-3 mg / 100 ml.

7. Use of borneol water containing a high natural borneol content prepared by the preparation method according to any one of claims 1 to 6 in preparing a preparation for treating infantile eczema.

8. Use of borneol water containing a high natural borneol content prepared by the preparation method according to any one of claims 1 to 6 in preparing a preparation for treating pruritus associated with chronic kidney disease.

9. Use of borneol water containing a high natural borneol content prepared by the preparation method according to any one of claims 1 to 6 in the preparation of a preparation for relieving / suppressing pain in gout patients during the acute outbreak period of gout.

10. The use according to any one of claims 7 to 9, characterized in that The content of natural borneol in the borneol water reaches 0.60±0.05g / 100ml, which is 5 times the content of natural borneol in saturated borneol water at room temperature, and the purity is ≥96%.