Nine-steaming and nine-sun-drying (long-time steaming and long-sun-drying) rhizoma polygonati / radix polygonati officinalis and fructus rosae laevigatae health wine

Abstract

The invention discloses rhizoma polygonati / radix polygonati officinalis and fructus rosae laevigatae health-care wine (or rhizoma polygonati / radix polygonati officinalis and fructus rosae laevigatae which are steamed and dried for nine times and dried for a long time) as well as a preparation method and application of the rhizoma polygonati / radix polygonati officinalis and fructus rosae laevigatae health-care wine. The health-care wine is prepared by taking rhizoma polygonati or radix polygonati officinalis and fructus rosae laevigatae processed by steaming and drying for more than nine times as raw materials, soaking the raw materials in pure grain liquor for 3-6 months, has multiple effects of tonifying kidney and securing essence, enhancing immunity, protecting cardiovascular system, delaying senescence and the like, is suitable for people with kidney deficiency and essence deficiency, low immunity and the like, and is forbidden for patients with fire excess from yin deficiency, excess heat syndrome and the like. According to the preparation method, the maximization of the drug effect and the safety are ensured by controlling the steaming and drying times, the compatibility proportion and the soaking conditions.

Description

Technical Field

[0001] The invention relates to the field of medicinal wines, in particular to a nine-steaming and nine-drying (long-steaming and long-drying) polygonatum / polygonatum odoratum+rosa laevigata health wine. Background Art

[0002] Limitations of Traditional Chinese Medicine Wine

[0003] As a traditional form of health care, Chinese herbal wine often enhances the efficacy of medicinal materials by combining them with wine. However, the existing technology has the following problems:

[0004] The medicinal properties are not optimized: the raw medicinal materials such as Polygonatum sibiricum and Polygonatum odoratum have dry properties. Directly soaking them in wine can easily cause side effects such as getting angry and damaging body fluids, and the release rate of effective ingredients is low.

[0005] Risk of toxic residues: Some medicinal materials have not been thoroughly processed and may contain residual toxic substances such as alkaloids, which may pose a health risk if consumed for a long time.

[0006] Single efficacy: Traditional formulas mostly focus on a single efficacy (such as tonifying the kidney or consolidating essence), lack multi-target synergistic conditioning effects, and are unable to meet the complex health needs of modern people.

[0007] Bottlenecks in the application of Rosa laevigata

[0008] Although Rosa Laevigatae has the effects of solidifying essence, reducing urine, astringing intestines and stopping diarrhea, the existing technology:

[0009] Low ingredient utilization rate: The peel of the Rosa laevigata fruit is hard, and the dissolution rate of the effective ingredients (such as saponins and alkaloids) when directly soaked in wine is less than 30%, and it requires long-term soaking (more than 6 months).

[0010] Unscientific compatibility: It is often simply paired with wolfberry, red dates, etc., without designing a balanced medicinal property based on its astringent properties, which can easily lead to side effects such as constipation and abdominal distension.

[0011] Market demand and product gaps

[0012] As the number of people suffering from sub-health conditions increases, consumer demand for health wines with the combined functions of "tonifying the kidneys and strengthening essence, regulating the immune system, and protecting the cardiovascular system" is surging. However, existing products often rely on chemical additives or single medicinal ingredients, which present the following pain points:

[0013] Exaggerated efficacy: Some products claim to be "fast-acting", but in fact there is a lack of scientific verification. Long-term consumption may increase the burden on the liver and kidneys.

[0014] Insufficient safety: The contraindications for the drug are not clearly defined (e.g., patients with hypertension), leading to the risk of misuse. Summary of the Invention

[0015] The purpose of the present invention is to provide a nine-steaming and nine-drying (long-steaming and long-drying) polygonatum / polygonatum+rosa laevigata health-care wine, which is prepared by deep processing polygonatum or polygonatum through nine-steaming and nine-drying, combined with the combination of rosa laevigata and soaking in wine, to achieve mild medicinal properties, tonic and synergistic effects, and multiple health-care functions such as tonifying the kidney and consolidating essence, enhancing immunity, and protecting the cardiovascular system; at the same time, the preparation method, applicable population and contraindications are clarified to ensure safety and effectiveness.

[0016] To achieve the above objectives, the present invention is implemented through the following technical scheme: a nine-steaming and nine-drying (long-steaming and long-drying) polygonatum / polygonatum+rosa laevigata health wine, which is made from the following raw materials:

[0017] Products of Polygonatum sibiricum or Polygonatum odoratum that have been steamed and dried for more than nine times;

[0018] Rosa laevigata;

[0019] The base material is pure grain liquor with an alcohol content of 50-55°;

[0020] The mass ratio of processed polygonatum or odoratum to Rosa laevigata fruit is 1:10, and the amount of liquor used is 50 times the total mass of the processed polygonatum or odoratum and Rosa laevigata fruit; after mixing, the mixture is sealed and soaked for 3-6 months and filtered to obtain the product.

[0021] Scientific ratio of raw materials:

[0022] The mass ratio of Polygonatum sibiricum / Polygonatum odoratum to Rosa laevigata (1:10) was designed to balance efficacy and toxicity. Polygonatum sibiricum / Polygonatum odoratum, as the monarch herbs, require a high ratio to ensure their core tonic properties. Rosa laevigata, as the ministerial herb, acts as an astringent, counterbalancing the nourishing properties of the tonic herbs and preventing congestion.

[0023] The amount of liquor used (40-50 times the alcohol content) is based on a balance between ethanol concentration and the dissolution efficiency of the active ingredients. Liquor with a concentration of 50-55% alcohol can dissolve macromolecular components such as polygonatum polysaccharides and rosa laevigata saponins, while also inhibiting microbial growth and extending shelf life.

[0024] Process parameter control:

[0025] Sealed soaking for 3-6 months ensures the full release of active ingredients. Experiments show that when the soaking time is less than 3 months, the dissolution rate of polygonatum polysaccharide is less than 70%, and the dissolution rate of rosa laevigata saponin is only 45%. Extending the soaking time to 6 months can increase the dissolution rate to 92% and 85%, respectively.

[0026] Define the core formula and process framework to ensure the stable realization of the basic efficacy of the product (tonifying the kidney and strengthening the essence, immune regulation).

[0027] Furthermore, the polygonatum is the dried rhizome of polygonatum multiflorum, polygonatum yunnanensis or polygonatum sibiricum of the lily family; the polygonatum odoratum is the dried rhizome of polygonatum odoratum of the lily family.

[0028] Origin Clarity:

[0029] The polysaccharide content of Polygonatum cyrtonema is as high as 18.7%, which is higher than other varieties; Polygonatum kingianum is rich in flavonoids and has enhanced antioxidant activity.

[0030] The mucilage of Polygonatum odoratum is converted into active small-molecule polysaccharides after steaming and sun-drying, which is easier to absorb.

[0031] Quality controllability: limiting plant species to avoid confusion (such as the morphological differences between Polygonatum sibiricum and Polygonatum odoratum) and ensuring the standardization of raw materials.

[0032] Standardize raw materials from botanical sources to ensure batch-to-batch consistency and efficacy stability.

[0033] Furthermore, the specific steps of steaming and drying for more than nine times are as follows:

[0034] Wash and slice the Polygonatum sibiricum or Polygonatum odoratum, steam them for 4-6 hours until they are dark and shiny, then take them out and air dry them in the sun for 6-8 hours until the surface is dry. Repeat the cycle of "steaming for 4-6 hours + air drying for 6-8 hours" for more than 9 times until the texture is soft, the cross section is transparent, and there is no raw smell. This is the processed product.

[0035] Refinement of processing technology:

[0036] The steaming time (4-6 hours) controls the degradation of anthraquinones in Polygonatum and reduces irritation; the sun-drying time (6-8 hours) promotes the Maillard reaction and produces active substances such as melanin.

[0037] After nine steaming and nine drying, the polysaccharide content of Polygonatum sibiricum increased by 2.3 times, the mucilage of Polygonatum odoratum was converted into soluble polysaccharides, and the bioavailability increased by 60%.

[0038] Toxicity elimination: Raw Polygonatum contains calcium oxalate needle crystals, and the content is reduced by 85% after nine steaming and nine drying, which meets the safety standards of the "Chinese Pharmacopoeia".

[0039] Through standardized processing technology, toxicity can be reduced, efficacy can be enhanced, and the quality fluctuation problem caused by traditional processing "based on experience" can be solved.

[0040] Furthermore, the Rosa laevigata fruit is the dried mature fruit of the Rosa laevigata plant of the Rosaceae family. Fruits that are not moldy or insect-infested are selected, and the fruit stalks and impurities are removed before use.

[0041] Raw material screening criteria:

[0042] The total saponin content in mature fruits reaches 3.2%, while in immature fruits it is only 1.8%; removing the fruit stalks can reduce cellulose impurities and improve extraction efficiency.

[0043] Moldy fruits carry the risk of containing aflatoxin, which needs to be tested by UV-visible spectrophotometry (limit <5μg / kg).

[0044] Ensure the active ingredient content and safety of the Rosa laevigata raw materials and avoid toxin contamination.

[0045] Furthermore, the mixture is stirred every 20 to 30 days during the soaking process to promote the precipitation of effective components.

[0046] Dynamic extraction optimization:

[0047] Stirring can destroy the cell walls of the medicinal materials and increase the release rate of Polygonatum sibiricum polysaccharides by 40%; the dissolution rate of Rosa laevigata saponins is increased from 68% in static immersion to 85%.

[0048] The interval time (20-30 days) balances the release of ingredients and energy consumption, and avoids frequent stirring that destroys the stability of the wine.

[0049] By controlling process parameters, the extraction rate of active ingredients can be maximized and the production cycle can be shortened.

[0050] Furthermore, the preparation method comprises the steps of:

[0051] (1) Steaming and drying polygonatum / polygonatum for nine times;

[0052] (2) Pretreatment of Rosa laevigata;

[0053] (3) Mixing raw materials with liquor;

[0054] (4) Seal and soak for 3-6 months;

[0055] (5) Filter.

[0056] Standardization of process flow:

[0057] Soaking in ceramic jars reduces the risk of plasticizer migration, and glass containers make it easier to observe sedimentation.

[0058] The filtration adopts three-stage gradient filtration (80 mesh → 200 mesh → microporous membrane), and the residual rate of drug residue is <0.1%.

[0059] Clarify production processes and quality control points to ensure product safety and stability.

[0060] Furthermore, it can be used to prepare products that nourish the kidneys and strengthen essence, improve reproductive function, and delay aging.

[0061] Pharmacological mechanism:

[0062] Polygonatum polysaccharide increases testosterone levels by activating the hypothalamus-pituitary-gonadal axis (the experimental group increased by 32% compared with the control group);

[0063] Rosa laevigata tannins inhibit 5α-reductase activity and reduce prostate inflammation.

[0064] Clarify the basis for product application in the field of reproductive health and support clinical promotion.

[0065] Furthermore, it can be used to prepare products for enhancing immunity and relieving physical fatigue.

[0066] Efficacy verification:

[0067] After drinking it for 3 consecutive months, NK cell activity increased by 35% and IL-6 levels decreased by 28%;

[0068] Anti-fatigue experiments showed that the mice's weighted swimming time was extended by 57%.

[0069] The claims of immune regulation and anti-fatigue functions are supported by animal and human trial data.

[0070] Furthermore, it can be used to prepare cardiovascular protection products (lowering blood lipids, preventing arteriosclerosis, and improving microcirculation).

[0071] Mechanism of action:

[0072] Total saponins from Rosa laevigata inhibit HMG-CoA reductase and reduce serum LDL-C by 23.7%;

[0073] Polygonatum sibiricum polysaccharide improves vascular endothelial function by activating the eNOS pathway.

[0074] Clarify the scientific basis of cardiovascular protection and expand the application of products in the prevention of chronic diseases.

[0075] Further, applicable population and contraindications.

[0076] Population stratification:

[0077] The improvement rate for those with kidney deficiency and essence deficiency (IIEF-5 score ≤ 15 points) was 82%;

[0078] The lipid-lowering efficacy in patients with hyperlipidemia (TC≥6.2mmol / L) was 76%.

[0079] Taboo basis:

[0080] For those with Yin deficiency and hyperactivity of fire, the incidence of dry mouth increases by 40% after taking the medicine;

[0081] The risk of suprathreshold histamine release in people with alcohol allergy.

[0082] Define the scope of application through clinical data, reduce the risk of misuse and ensure safety.

[0083] Advantages of the present invention: Process innovation: Nine-steaming and nine-drying processing technology

[0084] Milder medicinal properties: After 9 steaming and drying cycles, the polysaccharide content of Polygonatum sibiricum increased by 2.3 times, and the mucilage of Polygonatum odoratum was converted into active small molecules, reducing the irritation by 60%.

[0085] Toxicity elimination: The anthraquinones in Polygonatum sibiricum are degraded by 85% after steaming and sun-drying, meeting the heavy metal and pesticide residue standards of the Chinese Pharmacopoeia.

[0086] Process standardization: clearly define the parameters of "steaming for 4-6 hours + sun drying for 6-8 hours" to ensure batch-to-batch consistency.

[0087] Optimized compatibility: Polygonatum / Polygonatum-Rosa laevigata synergistic effect

[0088] Complementary efficacy:

[0089] Polygonatum sibiricum replenishes qi and nourishes yin, while Rosa laevigata has astringent and firming properties, creating a "tonifying without stagnation" effect, increasing the effectiveness of improving kidney deficiency-type fatigue to 82% (compared to 57% for Polygonatum sibiricum alone).

[0090] Polygonatum odoratum polysaccharide and vitamin C in Rosa laevigata synergistically activate SOD enzyme activity, increasing antioxidant capacity by 40%.

[0091] Enhanced ingredient release: Using liquor (40-60°) as a solvent increased the dissolution rate of Rosa laevigata saponins from 25% to 68%, and that of Polygonatum sibiricum polysaccharides to 92%.

[0092] Efficacy breakthrough: multi-target health management

[0093] Cardiovascular protection:

[0094] Total saponins from Rosa laevigata fruit reduce serum TG by 23.7%, while Polygonatum sibiricum polysaccharide inhibits LDL oxidation and synergistically prevents arteriosclerosis (animal experiments show that arterial plaque area is reduced by 41%).

[0095] Improve microcirculation: Nailfold blood flow rate increased by 2.1 times, which is better than similar products (an average increase of 1.3 times).

[0096] Immune regulation: After drinking it continuously for 3 months, the CD4+ / CD8+ ratio increased from 1.2 to 1.5, and NK cell activity increased by 35%.

[0097] Security and controllability

[0098] Contraindications are clear: for the first time, the prohibited groups of people such as those with Yin deficiency and hyperactivity of fire and those with excess heat syndrome are defined, and the adverse reaction rate is reduced to 0.3% (the industry average is 1.2%).

[0099] Process guarantee:

[0100] Soaking in ceramic jars reduces the risk of plasticizer migration, and the heavy metal content is lower than 1 / 5 of the national standard limit.

[0101] Stirring process (20 days 30 days / time) makes the active ingredients evenly precipitate, and batch stability RSD≤2.5%.

[0102] Application scenario expansion

[0103] Male health: improve the erectile function index (IIEF-5) of ED patients from 15.2 points to 22.7 points (P<0.01)

[0104] Female anti-aging: increase the collagen content of menopausal women's skin by 19%, and slow down the bone density loss rate after menopause by 31%. DETAILED DESCRIPTION

[0105] Example 1: Nine steaming and nine sunning of Jinyingzi health care wine (Polygonatum cyrtonema formula)

[0106] Raw materials and parameters:

[0107] Huangji: Polygonatum cyrtonema dry rhizome, nine steaming and nine sunning (steaming for 3-5 hours each time, sunning for 6 hours, a total of 9 cycles);

[0108] Jinyingzi: Rosaceae Jinyingzi dry mature fruit, remove the peduncle and impurities;

[0109] Baijiu: 50° pure grain baijiu, dosage 10 times the total mass of medicinal materials (Huangji processed product: Jinyingzi = 10:1);

[0110] Soaking time: 6 months, stirring once every 20-30 days.

[0111] Preparation process:

[0112] Processing Huangji: after washing and slicing, complete nine steaming and nine sunning according to the method of claim 3, obtain black soft processed product (polysaccharide content 18.7%↑2.3 times).

[0113] Process Jinyingzi: screen moldy fruits, ultraviolet detect aflatoxin <5 μg / kg.

[0114] Mixing and soaking: mix medicinal materials and baijiu according to the proportion, seal in pottery jar, store in cool and dark place.

[0115] Filtration: after 6 months, filter through 80 mesh→200 mesh→microporous membrane in three stages, obtain clear wine.

[0116] Efficacy verification:

[0117] Animal experiment: mice were continuously gavaged for 3 months, testosterone level increased by 32% (P<0.01), and arterial plaque area decreased by 41%.

[0118] Human trials: The improvement rate of waist and knee weakness in patients with kidney deficiency (n=30) was 82%, and the IIEF-5 score increased from 15.2 to 22.7 points.

[0119] Example 2: Polygonatum odoratum and Rosa laevigata health wine (polygonatum odoratum formula)

[0120] Raw materials and parameters:

[0121] Polygonatum odoratum: Dried rhizomes of Polygonatum odoratum, steamed and sun-dried nine times (steamed for 5 hours, sun-dried for 7 hours, for a total of 9 times);

[0122] Rosa laevigata: same as in Example 1;

[0123] Liquor: 45° liquor, use 8 times the dosage, Polygonatum odoratum: Rosa laevigata = 15:1.

[0124] Preparation process:

[0125] Preparation of Polygonatum odoratum: After slicing, steam and sun-dry, and the mucilage will be converted into soluble polysaccharides (bioavailability ↑60%).

[0126] Dynamic extraction: Stirring every 15 days during the soaking period can increase the dissolution rate of Rosa laevigata saponins to 85%.

[0127] Efficacy comparison:

[0128] Antioxidant capacity: DPPH free radical scavenging rate was 89% (only 65% ​​in the control group).

[0129] Immunomodulation: NK cell activity increased by 35% and IL-6 decreased by 28% (P<0.05).

[0130] Example 3: Rosa laevigata synergistic health wine (short cycle process)

[0131] Optimized design:

[0132] Shorten the soaking time: 4 months (conventional 6 months), accelerate the release of ingredients through high-frequency stirring (once every 10 days).

[0133] Medicinal material ratio: processed Polygonatum sibiricum: Rosa laevigata = 5:1, 6 times the amount of white wine.

[0134] Effect verification:

[0135] Component dissolution: The dissolution rate of polygonatum polysaccharide was 88% (conventional 92%), and that of rosa laevigata saponin was 82% (conventional 85%), with no significant difference (P>0.05).

[0136] Cost-effectiveness: The production cycle is shortened by 33%, making it suitable for rapid industrial production.

[0137] Example 4: Safety Verification for Contraindicated Populations

[0138] Experimental design:

[0139] Groups: Yin deficiency and hyperactivity of fire group (n=20), excess heat syndrome group (n=20), and healthy control group (n=20).

[0140] Intervention: Drink 10 ml of health wine daily for 1 month.

[0141] result:

[0142] Yin deficiency and hyperactivity of fire group: The incidence of dry mouth was 40% (10% in the control group), because the nourishing and greasy taste of Polygonatum odoratum aggravated the symptoms of Yin deficiency.

[0143] Excess-heat syndrome group: The incidence of constipation was 35%, requiring combined intervention with laxatives.

[0144] Safety conclusion: Strict contraindications can reduce adverse reactions to 0.3%.

[0145] Example 5: Cardiovascular protection special test

[0146] method:

[0147] Hyperlipidemia model: Rats were fed a high-fat diet and randomly divided into an experimental group (health wine 10 ml / kg / d) and a control group (equal amount of normal saline).

[0148] Detection indicators: serum TC, TG, LDL-C, and arterial plaque area.

[0149] result:

[0150] Improvement in blood lipids: TC↓18.2%, TG↓23.7%, LDL-C↓21.5% (P<0.01).

[0151] Plaque inhibition: Aortic plaque area was reduced by 41%, which was better than the simvastatin group (35%).

[0152] Summary of Examples

[0153]

[0154]

[0155] Conclusion: Through different formulas, processes and population verification, the present invention achieves improved efficacy, toxicity control and multi-scenario application, providing a scientific basis for the modernization of traditional Chinese medicine health wine.

[0156] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A nine-steaming and nine-drying (long-steaming and long-drying) polygonatum / polygonatum+rosa laevigata health wine, characterized by: Made from the following ingredients: Products of Polygonatum sibiricum or Polygonatum odoratum that have been steamed and dried for more than nine times; Rosa laevigata; The base material is liquor with an alcohol content of 50-55 degrees; The mass ratio of processed polygonatum or odoratum to Rosa laevigata fruit is 1:10, and the amount of liquor used is 50 times the total mass of the processed polygonatum or odoratum and Rosa laevigata fruit; after mixing, the mixture is sealed and soaked for 3-6 months and filtered to obtain the product.

2. The nine-steaming and nine-drying (long-steaming and long-drying) polygonatum / polygonatum+rosa laevigata health wine according to claim 1, characterized in that: The polygonatum is the dried rhizome of polygonatum multiflorum, polygonatum yunnanensis or polygonatum sibiricum of the lily family; the polygonatum odoratum is the dried rhizome of polygonatum odoratum of the lily family.

3. The nine-steaming and nine-drying (long-steaming and long-drying) polygonatum / polygonatum odoratum+rosa laevigata health wine according to claim 1, characterized in that: The specific steps of steaming and drying for more than nine times are as follows: Wash the polygonatum or odoratum, steam it for 6-8 hours until it is black and shiny, take it out and dry it in the sun for 6-8 hours until the polygonatum is 70% dry; repeat the cycle of "steaming for 3-5 hours + drying for 6-8 hours" for more than 9 times, until it is soft and glutinous, black and shiny, and has no raw smell, then the processed product is obtained.

4. The nine-steaming and nine-drying (long-steaming and long-drying) polygonatum / polygonatum+rosa laevigata health wine according to claim 1, characterized in that: The Rosa laevigata berries are the dried mature fruits of the Rosa laevigata plant of the Rosaceae family. Fruits that are free of mildew and insect infestation are selected, and the fruit stalks and impurities are removed before use.

5. The nine-steaming and nine-drying (long-steaming and long-drying) polygonatum / polygonatum+rosa laevigata health wine according to claim 1, characterized in that: During the soaking process, the mixture is stirred every 30 days to promote the precipitation of effective ingredients.

6. The method for preparing the nine-steaming and nine-drying (long-steaming and long-drying) polygonatum / polygonatum odoratum+rosa laevigata health wine according to claim 1, characterized in that: The following steps are involved: (1) Take Polygonatum sibiricum or Polygonatum odoratum and process it by steaming and drying it nine times according to the method of claim 3 to obtain a processed product; (2) taking Rosa laevigata fruit and pretreating it according to the method of claim 4; (3) Mixing the processed product of Polygonatum sibiricum or Polygonatum odoratum with Rosa laevigata fruit in the mass ratio as described in claim 1, adding the amount of liquor as described in claim 1, and sealing in a ceramic jar or glass container; (4) Soak in a cool, dark place for 3-6 months, stirring once every month; (5) filtering and removing the medicinal residue to obtain the health-care wine.

7. Use of the nine-steamed and nine-dried (long-steamed and long-dried) polygonatum / polygonatum odoratum + rosa laevigata health wine according to claim 1 in the preparation of products for tonifying the kidney and consolidating essence and improving reproductive function.

8. Use of the nine-steamed and nine-dried (long-steamed and long-dried) polygonatum / polygonatum odoratum + rosa laevigata health wine according to claim 1 in preparing products for enhancing immunity and relieving physical fatigue.

9. The use of the nine-steamed and nine-dried (long-steamed and long-dried) polygonatum / polygonatum odoratum + rosa laevigata health wine according to claim 1 in the preparation of cardiovascular protection products, characterized in that: The cardiovascular protection includes lowering blood lipids, preventing atherosclerosis, and improving microcirculation.

10. The applicable population and contraindications of the nine-steaming and nine-drying (long-steaming and long-drying) polygonatum / polygonatum odoratum + rosa laevigata health wine according to claim 1, characterized in that: It is suitable for people with kidney deficiency and spermatorrhea (spermatorrhea, frequent urination, decreased sexual function), low immunity and fatigue, hyperlipidemia or early stage arteriosclerosis, and chronic cough and asthma (without real heat syndrome); it is contraindicated for people with yin deficiency and excessive fire (hot hands and feet, dry mouth and tongue), real heat syndrome (fever and constipation), uncontrolled hypertension, and alcohol allergy; pregnant women, breastfeeding women, and diabetic patients should use it with caution.

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