阅读说明：本技术 含有腰果叶提取物的组合物及其产生方法 (Composition containing cashew nut leaf extract and its production method ) 是由 佩图·曼尼帕罗 于 2019-08-01 设计创作，主要内容包括：一种含有腰果叶提取物的组合物包含至少腰果叶提取物、硬脂酸镁和麦芽糖糊精,其中所述腰果叶提取物通过水或醇或者醇与水或其他有机溶剂的组合或者它们的组合来提取,优选地是水醇提取物。所述含有腰果叶提取物的组合物可以被用作滋补剂和/或适应原剂,以增强男性性功能的效率、增强男性性生育能力、改善认知功能。根据本发明的含有腰果叶提取物的组合物旨在增加腰果叶的商业化价值,所述腰果叶富有来自其中所含的若干营养物的健康有益效果,诸如增强与单胺尤其是多巴胺有关的神经系统的功能,所述单胺增强男性性功能并且还改善认知功能。(A composition containing cashew nut leaf extract comprises at least cashew nut leaf extract, magnesium stearate and maltodextrin, wherein said cashew nut leaf extract is extracted by water or alcohol or a combination of alcohol and water or other organic solvent or a combination thereof, preferably a hydroalcoholic extract. The composition containing cashew nut leaf extract can be used as a tonic and/or adaptogen to enhance the efficiency of male sexual function, enhance male sexual fertility, improve cognitive function. The composition containing the cashew nut leaf extract according to the invention is intended to increase the commercial value of cashew nut leaves which are rich in health benefits from several nutrients contained therein, such as enhancing the function of the nervous system associated with monoamines, in particular dopamine, which enhance male sexual function and also improve cognitive function.)

1. A composition comprises cashew nut leaf extract, magnesium stearate and maltodextrin.

2. The cashew nut leaf extract-containing composition of claim 1 having the following contents:

-cashew leaf extract 50-90% w/w

-magnesium stearate 5-20% w/w

-maltodextrin 5-30% w/w.

3. The cashew leaf extract-containing composition of any one of claims 1 or 2, wherein the composition can further comprise a pharmaceutically acceptable carrier.

4. The cashew nut leaf extract-containing composition of any of claims 1-3, wherein cashew nut leaf extract is extracted by water or alcohol or a combination of alcohol and water or other organic solvent or a combination thereof.

5. The cashew leaf extract-containing composition of any one of claims 1-4, wherein the extract is a hydroalcoholic extract.

6. The cashew leaf extract-containing composition of any one of claims 1-5, wherein the extract is obtained from a process using an organic solvent.

7. The cashew nut leaf extract-containing composition of any one of claims 1-6, wherein the composition can be used as a tonic and/or an adaptogen.

8. The cashew leaf extract-containing composition of any one of claims 1-6, wherein the composition can be used to enhance the efficiency of male sexual function.

9. The cashew nut leaf extract-containing composition of any one of claims 1-6, wherein the composition can be used to enhance male sexual fertility.

10. The cashew leaf extract-containing composition of any one of claims 1-6, wherein the composition can be used to improve cognitive function.

11. A method for producing a composition containing a cashew nut leaf extract comprises the steps of;

a. each component of the composition formulation described below was weighed: cashew leaf extract, magnesium stearate and maltodextrin, then mixing all components in a clean blender at a rate of 100 revolutions per minute for at least 30 minutes until the mixture powder is homogenous, then drying the mixture powder at 70 degrees celsius for 2-5 hours, then cooling at room temperature, then adding the mixture powder to capsules by a semi-automatic capsule filling machine, or storing in vacuum aluminum bags at-20 degrees celsius

b. Weighing the prepared mixture powder according to the number of capsules, then dividing the capsules into a body part and a lid part, then dispensing each part into a specific tray, which is a part of a capsule filling machine, then pouring and spreading the mixture powder into the body part of a capsule until the mixture is completely in the body part arranged on the tray, then compacting with a compactor, which is a part of the capsule filling machine until the mixture powder is completely filled into the body part, then assembling the compacted capsule body part containing cashew leaf extract with the lid part of the capsule arranged on the tray, then sieving the capsules on a sieve to remove dust, then storing the capsules in a dry opaque plastic package, quality tests were then carried out according to United States Pharmacopeia (USP) according to United states Pharmacopeia national formulary 2017 (USP 40NF 35) volume 1.

12. A food, beverage or food supplement or nutraceutical comprising a composition according to any one of claims 1 to 11.

13. The food, beverage or food supplement or nutraceutical according to claim 12, wherein the food, beverage or food supplement or nutraceutical may be in the form of a tablet, capsule, effervescent granule or tablet, granule, powder, gel, jelly, chewing gum, candy, spray, film, patch, cream, ointment, emulsion, or the like.

Technical Field

The present invention relates to the field of compositions containing cashew (Anacardium occidentale) leaf extract, which can be used in dietary supplements to increase testosterone levels in humans and to improve sexual performance and anti-stress ability.

Background

Cashew (Anacardium occidentale Linn) is a tropical plant distributed in Latin America and southeast Asia. Cashew leaves are commonly used as vegetables in thailand due to their special taste and high vitamin C and beta-carotene content. Cashew leaf has been used as a traditional drug for the treatment of sexual dysfunction and sexually transmitted diseases in west africa and latin america, but there are no reports or patents concerning the potential use of cashew leaf extract or the active ingredients in cashew leaf extract for the field.

The present invention aims to improve the health benefits of cashew leaf extract by combining with some additional compounds that are able to control the release of active compounds when cashew leaf extract is encapsulated.

Disclosure of Invention

A composition containing cashew nut leaf extract comprises at least cashew nut leaf extract, magnesium stearate and maltodextrin, wherein said cashew nut leaf extract is extracted by water or alcohol or a combination of alcohol and water or other organic solvent or a combination thereof, preferably a hydroalcoholic extract. The composition containing cashew nut leaf extract can be used as tonic and/or adaptogenic agent to enhance the efficiency of male sexual function, enhance male sexual fertility, and improve cognitive function.

The composition containing the cashew nut leaf extract according to the invention is intended to increase the commercial value of cashew nut leaves which are rich in health benefits from several nutrients contained therein, such as enhancing the function of the nervous system associated with monoamines, in particular dopamine, which enhance male sexual function and also improve cognitive function.

Drawings

Figure 1 effect of hydroalcoholic extract of cashew leaf extract on serum testosterone levels in rats exposed to stress after 7 and 14 days of treatment. Data are expressed as mean ± s.e.m. (n is 6/group). A value of<0.05, 0.01 and 0.001; compare to vehicle + stress.^###P value<0.001; and comparing with a control group.

Figure 2 effect of hydroalcoholic extract of cashew leaf extract on serum corticosterone levels in rats exposed to stress after 7 and 14 days of treatment. Data are expressed as mean ± s.e.m. (n is 6/group). P value<0.05 and 0.01; compare to vehicle + stress.^##,###P value<0.01 and 0.001; comparing with control group

Figure 3 effect of hydroalcoholic extract of cashew leaf extract on tyrosine hydroxylase immunoreactive neurons in ventral tegmental area of rats exposed to stress. Data are expressed as mean ± s.e.m. (n-6/group). Value of P<0.05 and 0.001; compare to vehicle + stress.^#P value<0.05; and comparing with a control group.

Figure 4 effect of hydroalcoholic extracts of cashew leaf extract on tyrosine hydroxylase immunoreactive neurons in the nucleus and shell of nucleus accumbens of rats exposed to stress. Data are expressed as mean ± s.e.m. (n is 6/group).^*,**,***P value<0.05, 0.01 and 0.001; compare to vehicle + stress.^#,##P value<0.05 and 0.01;

FIG. 5 Effect of hydroalcoholic extracts of cashew leaf extract on phosphodiesterase-5 activity in the penis of rats exposed to stress. Data are expressed as mean ± s.e.m. (n is 6/group).^*,**,***P value<0.05, 0.01 and 0.01; compare to vehicle + stress.^#P value<0.05; comparing with control group

FIG. 6 hydroalcoholic extract of cashew leaf extract to monoamine in the medial preoptic area and nucleus accumbens of rats exposed to stressInfluence of oxidase-B. Data are expressed as mean ± s.e.m. (n is 6/group).^*,***P value<0.05 and 0.001; compare to vehicle + stress.^#,###P<0.05 and 0.001; comparing with control group

FIG. 7 effect of hydroalcoholic extract of cashew leaf extract on endothelial nitric oxide synthase in penis of rats exposed to stress. Data are expressed as mean ± s.e.m. (n is 5/group).^*P value<0.05; compare to vehicle + stress.^#P value<0.05; comparing with control group

Fig. 8 effect of hydroalcoholic extracts of cashew leaf extract on ride delay in rats exposed to stress at baseline after single dose treatment for 7 and 14 days. Data are expressed as mean ± s.e.m. (n is 6/group).^*,**,***P value<0.05, 0.01 and 0.001; compare to vehicle + stress.^#,##,###P value<0.05, 0.01 and 0.001; comparing with control group

Fig. 9 effect of hydroalcoholic extract of cashew leaf extract on number of rides in rats exposed to stress at baseline after single dose treatment for 7 and 14 days. Data are expressed as mean ± s.e.m. (n is 6/group).^*P value<0.05; comparison with vehicle + stress

Fig. 10 effect of hydroalcoholic extract of cashew leaf extract on insertion delay of rats exposed to stress at baseline after single dose treatment for 7 and 14 days. Data are expressed as mean ± s.e.m. (n is 6/group).^*,**,***P value<0.05, 0.01 and 0.001; compare to vehicle + stress.^#,##,###P value<0.05, 0.01 and 0.001; and comparing with a control group.

Fig. 11 effect of hydroalcoholic extract of cashew leaf extract on number of insertions of rats exposed to stress at baseline after single dose treatment for 7 and 14 days. Data are expressed as mean ± s.e.m. (n is 6/group).^*,**P value<0.05 and 0.01; compare to vehicle + stress.^#,##P<0.05 and 0.01; comparing with control group

FIG. 12 after 7 and 14 days of single dose treatmentAt baseline, the effect of hydroalcoholic extracts of cashew leaf extract on ejaculation delay in rats exposed to stress. Data are expressed as mean ± s.e.m. (n is 6/group). P value<0.05; compare to vehicle + stress.^#,##P value<0.05 and 0.01; comparing with control group

Fig. 13 effect of hydroalcoholic extract of cashew leaf extract on ejaculation frequency in rats exposed to stress at baseline after single dose treatment for 7 and 14 days. Data are expressed as mean ± s.e.m. (n is 6/group).^*,**P value<0.05 and 0.01; compare to vehicle + stress.

Fig. 14 effect of ethanol extract of cashew nut leaf extract on human sperm. Values are mean ± s.d.

FIG. 15 effect of hydroalcoholic extract of cashew leaf extract on tissue morphology of hematoxylin and eosin (H & E) stained rat testes. The cross-sectional photographs show 1) convoluted seminiferous tubules (40-fold magnification), and 2) Leydig (Leydig) stromal cells (100-fold magnification), Sertoli (Sertoli) cells (SC), Spermatogonia (SG), Primary Spermatocytes (PS), Spermatids (SP), sperm, and Leydig Cells (LC) in the following treatment groups: A) initial controls, B) vehicle + stress, C) sildenafil citrate 5mg/kg + stress, D) tianeptine 15mg/kg + stress, E) -G) cashew + stress at doses of 25, 100 and 200mg/kg, respectively.

Detailed Description

A composition containing cashew nut leaf extract comprises at least cashew nut leaf extract, magnesium stearate and maltodextrin, wherein each component has the following content;

-cashew leaf extract 50-90% w/w

-magnesium stearate 5-20% w/w

-maltodextrin 5-30% w/w

The composition containing the cashew nut leaf extract according to the invention further comprises a pharmaceutically acceptable carrier.

The composition containing cashew nut leaf extract according to the invention, wherein the cashew nut leaf extract is extracted by water or alcohol or a combination of alcohol and water (hydroalcoholic extract) or other organic solvent or a combination thereof, preferably the hydroalcoholic extract. The extract is obtained from a process using an organic solvent.

A method for producing a composition containing a cashew nut leaf extract comprises the steps of;

a. each component of the composition formulation described below was weighed: cashew leaf extract, magnesium stearate and maltodextrin, then mixing all components in a clean blender at a rate of 100 revolutions per minute for at least 30 minutes until the mixture powder is homogenous, then drying the mixture powder at 70 degrees celsius for 2-5 hours, then cooling at room temperature, then adding the mixture powder to capsules by a semi-automatic capsule filling machine, or storing in vacuum aluminum bags at-20 degrees celsius

b. Weighing the prepared mixture powder according to the number of capsules, then dividing the capsules into a body part and a lid part, then dispensing each part into a specific tray, which is a part of a capsule filling machine, then pouring and spreading the mixture powder into the body part of the capsules until the mixture is completely in the body part arranged on the tray, then compacting with a compactor, which is a part of the capsule filling machine, until the mixture powder is completely filled into the body part, then assembling the compacted capsule body part containing cashew leaf extract with the lid part of the capsules arranged on the tray, then sieving the capsules on a sieve to remove dust, then storing the capsules in a dry opaque plastic package, quality tests were then carried out according to United States Pharmacopeia (USP) according to U.S. Pharmacopeia National Formulary 2017 (National Formulary 2017 of U.S. Pharmacopeia (USP 40NF 35) Vol.1.

The invention discloses a composition containing a hydroalcoholic extract of cashew (Anacardium occidentale) leaves. In the present invention, the components of the cashew leaf extract are identified as quercetin, myricetin, catechin, epicatechin, amentoflavone, tetramer of procyanidins, quercetin glycoside, rutin, tannin, alkaloid and saponin. It was found that the stability of the extract is high even if the extract is stored at temperatures above room temperature. More importantly, the biological activity of the extract changes slightly under high temperature conditions.

Cashew leaf extract is considered to be very low in toxicity or safe to eat, with LD50 greater than 2 grams per kilogram of body weight. Toxicity studies were performed in animal models of male and female rats. Toxicity test results are shown in tables 1-14.

Table 1 body weight of rats fed cashew nut leaf extract at a dose of 2 g/kg body weight.

Table 2 weight of internal organs of male rats fed with cashew nut leaf extract at a dose of 2 g/kg body weight.

Table 3 weight of internal organs of female rats fed cashew nut leaf extract at a dose of 2 g/kg body weight.

TABLE 4 histological changes in male rats fed with cashew leaf extract at a dose of 2 g/kg body weight

P values of 05 and 001, respectively, compared to treatment

TABLE 5 histological changes in male rats fed with cashew leaf extract at a dose of 2 g/kg body weight

TABLE 6 clinical chemistry Change in Male rats fed with cashew leaf extract at a dose of 2 g/kg body weight

P values of 05 and 01, respectively, were compared to treatment

TABLE 7 clinical chemistry Change in female rats fed cashew leaf extract at a dose of 2 g/kg body weight

P values of 05 and 01, respectively, were compared to treatment

As shown in table 8, the sub-chronic toxicity study of cashew leaf extract according to the invention showed no significant growth in both male and female rats. Furthermore, as shown in table 9, the weight of the internal organs of male rats did not change significantly, but as shown in table 10, female rats fed with 100mg extract/kg body weight both the weight of the brain and the size of the stomach were significantly reduced.

Table 8 body weights of rats (n-15/group) fed cashew leaf extract at doses of 20, 100, 500 mg/kg body weight for 90 days.

Table 9 internal organ weights (n-15/group) of male rats fed with cashew leaf extract at doses of 20, 100, 500 mg/kg body weight for 90 days.

Table 10 internal organ weights of female rats fed with cashew leaf extract at doses of 20, 100, 500 mg/kg body weight for 90 days (n-15/group).

Table 11 histological changes of male rats fed with cashew leaf extract at doses of 20, 100, 500 mg/kg body weight for 90 days (n-15/group).

Table 12 histological changes of female rats fed with cashew leaf extract at doses of 20, 100, 500 mg/kg body weight for 90 days (n-15/group).

As shown in tables 11 and 12, cashew leaf extract can cause some changes in histological indicators, but they are all within the normal range.

Table 13 clinical chemistry data (n-15/group) of 90 day male rats fed cashew leaf extract at doses of 20, 100, 500 mg/kg body weight.

Table 14 clinical chemistry data (n-15/group) of 90 day male rats fed cashew leaf extract at doses of 20, 100, 500 mg/kg body weight.

Biological activity of cashew leaf extract:

as shown in tables 13 and 14, cashew nut leaf extract showed strong activity on triglyceride level reduction in male rats compared to control rats, but not in female rats when fed with the cashew nut leaf extract at concentrations of 20, 100 and 200mg/kg body weight. Furthermore, there was no significant change in the consumption of rats during the study of the present invention compared to control rats.

Pharmacological activity of cashew extract

The cashew nut leaf extract according to the present invention shows pharmacological activity in enhancing the function of the nervous system associated with monoamines (especially dopamine) that enhance the sexual function of male rat population. As shown in figure 2, the activity is caused by inhibition of enzymes that inhibit monoamine (especially dopamine) function, testosterone increase, corticosterone decrease.

Furthermore, cashew leaf extract according to the invention can also increase the density of dopamine neuron cells in Ventral Tegmental Area (VTA) and nucleus accumbens (NAc) areas of the brain, as shown in fig. 3 and 4. The Ventral Tegmental Area (VTA) and nucleus accumbens (NAc) of the brain are responsible for libido.

In addition, as shown in fig. 5, the cashew nut leaf extract according to the present invention can also increase blood circulation causing penile erection by inhibiting phosphodiesterase type 5. The extract can also inhibit enzyme activity, including inhibition of monoamines (especially dopamine) in the medial pro-visual area (mPOA) and nucleus accumbens (NAc) (as shown in fig. 6), and increase the amount of endothelial nitric oxide synthase (eNOS) in the penis (as shown in fig. 7). Thus, it enhanced libido, as shown in FIGS. 8-13.

The cashew nut leaf extract according to the present invention is obtained from a hydroalcoholic extraction process with 95% ethanol or other extraction processes (e.g., supercritical fluid extraction, microwave extraction, or ultrasonic extraction or other similar methods).

1. The extract comprises phenolic or flavonoid compounds including gallic acid or rutin or quercetin or combinations thereof. The extract has a phenolic compound content in the range of 75 to 300 μ g GAE per milligram of extract and a flavonoid content in the range of 1 to 75 μ g quercetin per milligram of extract. It is important to note that the ratio of gallic acid to rutin to quercetin is in the range of 20-140:5-20: 0.05-10. In order to obtain pharmacological activity of the composition comprising the extract, the concentration of the extract is in the range of 100-500 mg/part.

The composition according to the invention may be used as a tonic and/or an adaptogen. The functions of tonics and adaptogens result from actions in multiple target organs, including but not limited to stress hormone or glucocorticoid reduction or sympathetic nerve enhancement.

The composition according to the invention may also be used to enhance the efficiency of male sexual function resulting from effects on multiple target organs including, but not limited to, increasing testosterone and/or increasing dopamine activity in the brain and/or inhibiting phosphodiesterase type 5 and/or reducing oxidative stress status and/or increasing nitric oxide formation in male sexual organs.

The composition according to the invention may also be used to enhance male sexual fertility. Male sexual fertility enhancement results from increased testosterone levels and/or decreased oxidative stress status and/or increased spermatogenesis in the male sexual organs.

The composition according to the invention may also be used for improving cognitive function. Cognitive function is improved by enhancing choline function and/or reducing oxidative stress states and/or neurogenesis and/or enhancing signaling through mitogen-activated protein kinases (MAPKs) in the brain.

Also included within the scope of the invention is a food, beverage or food supplement or nutraceutical consisting of said composition. The food, beverage or food supplement or health product according to the present invention may include, but is not limited to, food, beverage or food supplement or health product in the form of tablets, capsules, effervescent granules or tablets, granules, powders, gels, jellies, chewing gums, candies, sprays, films, patches, creams, ointments, emulsions, etc.

Although the invention has been disclosed in the context of certain embodiments and examples, it will be understood by those skilled in the art that the present invention extends beyond the specifically disclosed embodiments to other alternative embodiments and/or uses of the invention and obvious modifications and equivalents thereof. In addition, while several variations of the invention have been shown and described in detail, other modifications, which are within the scope of this invention, will be readily apparent to those of skill in the art in light of this disclosure. It is also contemplated that various combinations or sub-combinations of the specific features and aspects of the embodiments may be made and still fall within the scope of the invention. It should be understood that various features and aspects of the disclosed embodiments can be combined with or substituted for one another in order to form varying modes of the disclosed invention. Therefore, it is intended that the scope of the present invention herein disclosed should not be limited by the particular disclosed embodiments described above, but should be determined only by a fair reading of the claims that follow.