阅读说明：本技术 治疗便秘和其他胃肠系统疾病的组合物和方法 (Compositions and methods for treating constipation and other gastrointestinal disorders ) 是由 雅各布·拉杰菲尔 于 2020-02-05 设计创作，主要内容包括：一种治疗便秘和其他胃肠系统疾病的方法,包括在足够长的时间内施用药物有效量的组合物,所述组合物使得胃肠细胞中产生一氧化氮,并最终对治疗便秘和其他胃肠系统疾病产生有益效果。所述组合物包括姜或姜衍生物、巴西晃晃木和巴西香可可,刺激胃肠细胞中的一氧化氮以增加NO并改善胃肠细胞的功能。(A method of treating constipation and other gastrointestinal disorders comprising administering a pharmaceutically effective amount of a composition that produces nitric oxide in gastrointestinal cells for a sufficient period of time and ultimately has a beneficial effect in treating constipation and other gastrointestinal disorders. The composition includes ginger or a ginger derivative, agaricus blazei and agaricus tabacum, stimulates nitric oxide in gastrointestinal cells to increase NO and improves the function of the gastrointestinal cells.)

1. A method of treating constipation and other gastrointestinal system disorders comprising:

administering a pharmaceutically effective amount of a composition comprising ginger or a ginger derivative, agaricus brasiliensis and agaricus camaranthus, for a sufficient period of time to stimulate nitric oxide in gastrointestinal cells to increase NO and improve gastrointestinal cell function, produces nitric oxide in gastrointestinal cells and ultimately has a beneficial effect in treating constipation and other diseases of the gastrointestinal system.

2. The method of claim 1, wherein the composition comprises from 10mg to 3g ginger or a ginger derivative.

3. The method of claim 1, wherein the composition further comprises L-arginine, L-citrulline, or a mixture of L-arginine and L-citrulline.

4. The method of claim 3, wherein the composition comprises 10mg to 3g of L-arginine, L-citrulline, or a mixture of L-arginine and L-citrulline.

5. The method of claim 4, wherein the composition comprises 10mg to about 3g ginger or ginger derivative, 62.5mg to about 3g agarwood, and 62.5mg to 3g agaricus cocoa.

6. The method of claim 1, wherein the composition comprises 62.5mg to 3g of vesuvianite.

7. The method of claim 6, wherein the composition comprises 500mg to 1.5g of vesuvianite.

8. The method of claim 1, wherein the composition comprises 62.5mg to 3g guarana.

9. The method of claim 1, wherein the composition comprises 500mg guarana.

10. The method of claim 1, wherein the composition comprises 10mg to 3g ginger or ginger derivative, 62.5mg to 3g agarwood, and 62.5mg to 3g agaricus.

11. The method of claim 1, wherein the composition comprises 500mg ginger or ginger derivative, 500mg agaricus blazei and 500mg cacao.

12. The method of claim 1, wherein the composition comprises ginger or a ginger derivative, agaricus blazei murrill, and agaricus carameli.

13. The method of claim 12, wherein the composition comprises 10mg to 3g ginger or ginger derivative, 62.5mg to 3g agarwood, and 62.5mg to 3g agaricus.

14. The method of claim 13, wherein the composition comprises 500mg ginger or ginger derivative, 500mg agaricus blazei and 500mg cacao.

15. A pharmaceutical composition comprising:

an effective amount of ginger or a ginger derivative,

an effective amount of L-citrulline, L-arginine or a mixture of L-arginine and L-citrulline,

an effective amount of a woodenberg, an

An effective amount of guarana,

wherein the composition is administered in a periodic dose for a time sufficient to treat constipation and other gastrointestinal system disorders, the composition being in an oral dosage form comprising a tablet, capsule or lozenge.

16. The pharmaceutical composition of claim 15, wherein the composition comprises 10mg to 3g of L-arginine, L-citrulline, or a mixture of L-arginine and L-citrulline; 10mg to about 3g of ginger or a ginger derivative, 62.5mg to about 3g of agaricus blazei and 62.5mg to 3g of guarana.

17. The pharmaceutical composition of claim 16, wherein the composition comprises 1500mg or 1600mg of L-arginine, L-citrulline, or a mixture of L-arginine and L-citrulline; 500mg of ginger or a ginger derivative, 500mg of agaricus blazei murrill and 500mg of guarana camara.

18. A pharmaceutical composition comprising:

an effective amount of ginger or a ginger derivative,

an effective amount of a woodenberg, an

An effective amount of guarana,

wherein the composition is administered in a periodic dose for a time sufficient to treat constipation and other gastrointestinal system disorders, the composition being in an oral dosage form comprising a tablet, capsule or lozenge.

19. The pharmaceutical composition of claim 18, wherein the composition comprises 10mg to about 3g ginger or ginger derivative, 62.5mg to about 3g agarwood, and 62.5mg to 3g agaricus cocoa.

20. The pharmaceutical composition of claim 19, wherein the composition comprises 500mg ginger or ginger derivative, 500mg agaricus blazei and 500mg cacao.

Technical Field

The present invention relates to compositions and methods for treating constipation and other diseases of the gastrointestinal system.

Background

About 14% of all people worldwide are affected by constipation. In the united states, approximately 15% of adults and 30% of people over the age of 60 suffer from constipation, which is defined as a dry and hard stool or less than 3 stool times per week. The actual prevalence may be higher as many people believe their bowel habits are normal and report missing constipation symptoms. Furthermore, recent investigations evaluating current constipation medical management have shown that patients are not satisfied and conventional treatments are not considered to be the optimal treatment regimen because they lead to uncontrollable explosive stools. Before finding an effective treatment, a constipation patient will typically try about 4 over-the-counter drugs and 2 prescription drugs. Nevertheless, most patients report that their resulting remission is unacceptable.

In addition, constipation patients are reported to have a high rate of work absenteeism. Patients with constipation also had poorer overall health, mental health and social capacity than healthy controls. They also report that constipation interferes with pleasurable activities (e.g., family activities, school of children, or sporting events) and negatively impacts their confidence, ability to engage in ever preferred hobbies, partnership and intimacy, and work/employment or working ability.

Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder characterized by altered bowel habits and abdominal pain that adversely affect quality of life. IBS is subdivided into constipation-type (IBS-C), diarrhea-type (IBS-D) or mixed type (IBS-M). IBS is not curable and current treatment strategies often require patients to take multiple medications to control symptoms. Bulk purgatives (bulk agents), laxatives and antidiarrheals are used to help normalize changes in bowel habits, while tricyclic antidepressants and antispasmodics are intended to minimize visceral pain associated with the disease. The variable effectiveness of this symptomatic IBS treatment highlights the need for alternative approaches.

Disclosure of Invention

According to a first aspect, the present invention provides a method of treating constipation and other diseases of the gastrointestinal system. The method comprises administering a pharmaceutically effective amount of a composition that produces nitric oxide in the gastrointestinal cells for a sufficient period of time and ultimately produces beneficial effects in the treatment of constipation and other gastrointestinal system diseases. The composition includes ginger or a ginger derivative, muira puama (muira puama) and guarana puama (paulllinia cupana), which stimulate nitric oxide in gastrointestinal cells to increase NO and improve gastrointestinal cell function.

In some embodiments, the composition comprises 10mg to 3g ginger or ginger derivative.

In some embodiments, the composition further comprises L-arginine, L-citrulline, or a mixture of L-arginine and L-citrulline.

In some embodiments, the composition comprises 10mg to 3g of L-arginine, L-citrulline, or a mixture of L-arginine and L-citrulline.

In some embodiments, the composition comprises from 62.5mg to 3g of muirapuama.

In some embodiments, the composition comprises from 500mg to 1.5g of muirapuama.

In some embodiments, the composition comprises 62.5mg to 3g of guarana.

In some embodiments, the composition comprises 500mg guarana.

In some embodiments, the composition comprises 10mg to 3g of ginger or a ginger derivative, 10mg to 3g L-arginine, L-citrulline or a mixture of L-arginine and L-citrulline, 62.5mg to 3g of muirapuama and 62.5mg to 3g of guarana.

In some embodiments, the composition comprises 500mg of ginger or a ginger derivative, 1500mg or 1600mg of L-arginine, L-citrulline or a mixture of L-arginine and L-citrulline, 500mg of muirapuama and 500mg of Bacopa puama.

In another aspect, there is provided a pharmaceutical composition consisting of an effective amount of ginger or a ginger derivative, an effective amount of L-citrulline, L-arginine or a mixture of L-arginine and L-citrulline, an effective amount of muirapuama and an effective amount of cocoa basjorana. The composition is administered in a periodic dose for a time sufficient to treat constipation and other diseases of the gastrointestinal system, and is in an oral dosage form comprising a tablet, capsule or lozenge.

In another aspect, a pharmaceutical composition is provided consisting of an effective amount of ginger or a ginger derivative, an effective amount of agaricus blazei murrill, and an effective amount of cacao. The composition is administered in a periodic dose for a time sufficient to treat constipation and other gastrointestinal disorders, and is in an oral dosage form comprising a tablet, capsule or lozenge.

Additional advantages of the embodiments will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention. The advantages will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims.

Drawings

Figure 1 shows test data for bristol stool scores (p <0.01) and weekly stools (p <0.01) before and after treatment with a nutraceutical composition of the present invention.

FIG. 2 shows test data for defecation and abdominal pain before and after treatment with a nutraceutical composition of the present invention.

Figure 3 shows test data for defecation before and after application of a nutraceutical composition of the present invention.

Figure 4 shows test data for an average weekly stool increment from 2.7 to 7.3 before and after use within 2 to 4 weeks of application of the nutraceutical composition of the present invention with p < 0.0001.

Figure 5 shows test data for improved defecation perception before and after application of a nutraceutical composition of the present invention.

Figure 6 shows test data for bristol stool scores (p <0.001) increasing from 1.5 to 3.4 before and after application of a nutraceutical composition of the present invention.

FIG. 7 shows test data for the reduction in the number of abdominal pain patients before and after application of the present invention.

Detailed description of the preferred embodiments

Detailed embodiments of the present invention are disclosed herein. However, it is to be understood that the present invention may be embodied in various forms and that the embodiments disclosed herein are merely exemplary embodiments of the invention. Therefore, the details disclosed herein are not to be interpreted as limiting, but merely as the basis for teaching one skilled in the art how to make and/or use the invention.

The present invention provides compositions and methods for treating constipation and other gastrointestinal system disorders. According to a first embodiment, the present invention provides a nutraceutical composition (referred to herein and in the various figures as COMB-4) for the treatment of constipation and other gastrointestinal disorders, comprising an effective amount of ginger or a derivative selected from the group consisting of: fresh, partially dried ginger (ginger), dried ginger (dried ginger), 6-gingerol and mixtures thereof; at least one of arginine and citrulline (preferably L-arginine, L-citrulline, or a combination of L-arginine and L-citrulline); performing Brazilian shaking wood; and guarana (guarana).

It is well known that Nitric Oxide (NO) is a chemical substance that is important for the normal function of the mucosa (secretion of fluids into the faeces) and for the vascular tone of the gastrointestinal tissue. In addition, NO has recently been shown to be a neurotransmitter in the non-adrenergic, non-cholinergic (NANC) nerves of the human gut. Thus, NO from these NANC nerves is involved in the regulation of smooth muscle tissue tone, such as regulating intestinal motility, gastric emptying and antral motility. NO also regulates acid and gastric mucus secretion, base production, and is involved in maintaining mucosal blood flow (Nitin i.kochar, oil v.chandewal, Ravindra l.bakal and Priya n.kochar,2011. nitic Oxide and the Gastrointestinal tract.

As a systemic signaling molecule, NO activates soluble guanylate cyclase to form cGMP, which is a second messenger of the NO-cGMP pathway responsible for all the actions of NO in the gastrointestinal tract (Brasius, T.A., M.Field and D.V.Kimberg,1976. endogenous mucosal cyclic GMP: Regulation and relationship transport. am.J.Physiol.,231: 275-282). Nitric oxide donors, such as sodium nitroprusside, S-nitroso-N-acetylpenicillamine and isosorbide dinitrate, stimulate mucus secretion from ex vivo gastric cell suspensions (Brown, J.F., B.L.Tepperman, P.J.Hanson, B.J.Whittle and S.Moncada,1992.Differential distribution of nitrile oxide synthase beta cell fractions from the organic of the said salt structural bacteria, biochem. Biophy. Res.Commun.184: 680-. Dibutyryl cyclic GMP and cyclic GMP phosphodiesterase inhibitors M and B22948 also increase mucus release. Topical administration of the NOS inhibitor N-monomethyl-L-arginine reduces fluid secretion in patients with collagenous colitis (Perner, A., L. Andrescen, M. Normark, B. Fischer-Hansen, J. Rask-Madsen, J. Eugen-Olsen and J. Rask-Madsena,2001.Expression of nitric oxide synthases and effects of L-arginines and L-NMMA on nitric oxide production and fluid transport in collagen metabolism. guide, 49: 387-394).

As shown in applicants' previous work, COMB-4 is known to stimulate the NOS enzymes that produce NO in a variety of other cells; FOR example, COMB-4 stimulates iNOS in THE smooth muscle cells OF THE corpus cavernosum (see U.S. patent application publication No. 2014/0255528 entitled "COMPOSITIONS AND METHODS FOR TREATING, INHIBITING THE ONE SET, AND SLOWING THE PROGRESSION OF THE ERECTIVE DYSTRUCTION INPUTING NATURAL OCCURING GAGE RELATED ERECTILE DYSTRUCTION"), COMB-4 stimulates iNOS AND eNOS in THE bone (see U.S. patent application publication No. 2018/0104300 entitled "COMPOSITIONS AND METHODS FOR THE TREATMENT OF ORTHOPEDICAMENTS", incorporated herein by reference). Applicants' in vitro tests (shown below) indicate that COMB-4 is effective in promoting the production of NO by gastrointestinal cells and ultimately has beneficial effects in treating constipation and other diseases of the gastrointestinal system.

Evidence from human experiments and epidemiological studies indicate that exogenous NO has a protective effect on the gastrointestinal tract. The inflammatory response occurring in the gastrointestinal tract with Inflammatory Bowel Disease (IBD) is associated with induction of iNOS and increased NO production in the intestine. Although the exact effect of iNOS induction in these experimental settings is not clear, it has been demonstrated that NO is at least essential for healing and protecting intestinal lesions from certain inflammatory conditions. The main clinical features of IBS are changes in gut motility, secretion and visceral sensation. Although the underlying cause of IBS is unclear, it has been demonstrated that guanosine monophosphate (cGMP) is formed by NO activation of guanosine cyclase, which activates secretion of intestinal fluids. In fact, when using PDE5 inhibitors that up-regulate the NO-cGMP pathway in IBS, intestinal motility and secretion will be improved.

Given the individual components of the nutraceutical compositions of the present invention, ginger is a complex natural composition that, when used alone and/or in combination with other compounds, has a number of claimed properties. For example, some traditional Chinese medicines are used in compositions or added with ginger to treat or prevent various diseases for various reasons from the literature. However, in the past century, scientific approaches have shown that many traditional Chinese medicines do not produce so-called effects and/or may even worsen the target disease. However, some traditional Chinese medicines are found to contain active ingredients that may be useful in medicine, even if the purported use of the traditional Chinese medicine is not effective or safe. The complexity of ginger and its myriad characteristics are reflected in certain constituent compounds having the following structure:

among these, for example, in 6-gingerol, the R side chain of the vanillyl aldehyde functional group (i.e., 4-hydroxy-3-methoxyphenyl) is:

thus, 6-gingerol (also known as gingerol) is (S) -5-hydroxy-1- (4-hydroxy-3-methoxyphenyl) -3-decanone, having the following structure:

since ginger contains a variety of compounds, varying in complexity and chemical activity, there are conflicting teachings in the art regarding the biological activity of compounds that may contribute to the induction of nitric oxide production or have potential effects in therapy. Furthermore, there is still considerable unpredictability as to how to understand (let alone control) the relevant metabolic pathways.

As previously described, applicants have found that ginger is effective in treating constipation and other gastrointestinal system diseases when combined with agarwood, guarana, and at least one of arginine and citrulline, preferably L-arginine, L-citrulline, or a combination of L-arginine and L-citrulline.

The oral dosage form of the nutraceutical composition of the present invention is selected from the group consisting of tablets, capsules, lozenges, powders or suspensions comprising the above ingredients. The starting materials and component materials may be dried, for example by freeze-drying or vacuum-drying, prior to formulation into an oral dosage form. Individual dosage forms may include compressed tablets, capsules, lozenges or may be provided in a sachet. Suspension formulations may be provided. Ginger, ginger root extract, L-arginine, L-citrulline, agaricus blazei and agaricus cocoa (guarana) are all commercially available individually. Preferably, these ingredients are combined and encapsulated in gelatin capsules, but it is expected that other dosage forms will produce the same effect.

Flavorings or taste masking agents may be used. Tablets or other dosage forms may include diluents (e.g., lactose), disintegrants (e.g., croscarmellose sodium), or binders (e.g., polyvinylpyrrolidone). Lubricants, such as magnesium stearate, or other conventional excipients (e.g., silicon dioxide, carbohydrates, etc.) may be used. Film coated tablets may be provided.

The active ingredients of the compositions of the present invention are combined using well known standard methods and reagents. Preferably, the gelatin capsule comprises the combined ingredients in powder form. Standard ingredients in powder formulations are used to prepare and formulate the preferred exemplary formulations of the present invention. The powdered ingredients are inspected, weighed, mixed and encapsulated in gelatin capsules. The mixing process includes standard screening, mixing and heavy metal detection at standard temperatures and in a sterile environment at least sufficient for food addition.

Since certain preferred formulations of the nutraceutical compositions of the present invention include compounds found in or extracted from food products, they may be referred to as "nutraceuticals". While nutraceutical compositions have traditionally been presented in pharmaceutical forms, such as capsules or tablets, there is an increasing use of nutraceuticals for fortification of food products. The present invention uses analogs and/or homologs of ginger component in combination with guarana, L-arginine and/or L-citrulline to promote the production of nitric oxide in the gastrointestinal system sufficient to treat constipation and other gastrointestinal system diseases. While it is preferred to administer the nutraceutical composition in a gelatin capsule containing the ingredients of the nutraceutical composition, the nutraceutical composition of the present invention can be administered in a variety of ways and forms to cater for the lifestyle and dietary preferences of the user, such as once or twice daily dietary supplements, incorporation into food or "smoothies" and the like.

As used herein, "effective amount" refers to a sufficient dose of each ingredient contained in a dosage form of the nutraceutical composition when administered to a human patient for a sufficient time to treat constipation. In the case of treating constipation, the "beneficial effects" include at least one of an improvement in sense of complete excretion, an improvement in bristol stool score, a reduction in stress during defecation, and an increase in defecation frequency.

As used herein, an "individual dose" refers to the amount of nutraceutical composition in a single dose of the nutraceutical composition administered to a human patient as part of a dosing regimen.

As used herein, "total daily dose" refers to the cumulative amount of nutraceutical composition administered to a human patient over the course of a day, whether the nutraceutical composition is administered once daily or multiple times daily as part of a dosing regimen.

As used herein, "about" refers to a range of +/-10% of the stated value.

According to a preferred embodiment, the total daily dose of the nutraceutical composition is as follows:

from about 10mg to about 3g ginger or a ginger derivative,

about 187.5mg to about 3g L-citrulline, L-arginine, or a combination of L-arginine and L-citrulline,

about 62.5mg to about 3g (preferably about 500mg to about 1.5g) of vesuvianite, and

about 62.5mg to about 3g of guarana.

The specific individual doses forming the basis for the test results of the present invention (wherein the nutraceutical composition is taken twice daily) include:

about 250mg of ginger or a ginger derivative,

about 750mg (or 800mg, depending on the preparation method) of L-citrulline,

about 250mg of Woodfordia Brasiliensis, and

about 250mg of guarana (guarana).

This will therefore result in the preferred daily dose:

about 500mg of ginger or a ginger derivative,

about 1500mg (or 1600mg, depending on the preparation process) of L-citrulline,

about 500mg of Woodfordia Brasiliensis, and

about 500mg of guarana (guarana).

While it is preferred to administer the nutraceutical compositions of the present invention twice daily, it will be appreciated that other dosing regimens may be used to administer the nutraceutical compositions, and thus the individual doses will be adjusted so as not to exceed the preferred total daily dose as described above. Whether administered once or more times per day, are administered for a time sufficient to treat constipation.

Constipation and other gastrointestinal disorders may also be treated using variants of COMB-4 in which L-citrulline, L-arginine, or a combination of L-arginine and L-citrulline (referred to herein as COMB-3) is removed, according to alternative embodiments of the present invention. Preliminary experiments have shown that COMB-3, while not producing the beneficial effects consistent with COMB-4, does help treat constipation and other gastrointestinal system diseases. Removal of L-citrulline, L-arginine, or a combination of L-arginine and L-citrulline from the composition may reduce the size of pills and/or capsules required by the patient, which is believed to potentially make the patient more likely to take the required nutraceutical ingredients to significantly ameliorate constipation and other gastrointestinal system disorders.

According to this embodiment, the nutraceutical composition comprises an effective amount of ginger or a ginger derivative selected from the group consisting of fresh, partially dried ginger, 6-gingerol and mixtures thereof; performing Brazilian shaking wood; and guarana (guarana).

According to a preferred embodiment of the alternative nutraceutical composition, the total daily dose of said nutraceutical composition is:

from about 10mg to about 3g ginger or a ginger derivative,

about 62.5mg to about 3g (preferably about 500mg to about 1.5g) of vesuvianite, and

about 62.5mg to about 3g of guarana.

The specific individual doses of COMB-3 that form the basis of the test results described herein, wherein the nutraceutical composition is taken only once a day, comprise:

about 250mg of ginger or a ginger derivative,

about 250mg of Woodfordia Brasiliensis, and

about 250mg of guarana (guarana).

This will therefore result in the preferred daily dose:

about 500mg of ginger or a ginger derivative,

about 500mg of Woodfordia Brasiliensis, and

about 500mg of guarana (guarana).

The nutraceutical compositions include optional pharmaceutically acceptable excipients, fillers, binders and colorants, and can be packaged in standard gelatin capsules or formed into solid tablets, taken in granular form, or mixed and/or suspended in a solution.

The nutraceutical compositions of the present invention reflect the ability of the combination of ginger, guarana, and L-citrulline and/or L-arginine (or three nutraceutical compositions as described above) to treat constipation. The nutraceutical composition can be taken indefinitely to maintain the beneficial effect.

The efficacy of the nutraceutical compositions of the present invention in the treatment of constipation and other diseases of the gastrointestinal system was tested as follows.

Method

10 patients with severe constipation received COMB-4 (i.e., in each 70kg male, the composition of the present invention was administered at a dose of 500 mg/day ginger rhizome, 1500 mg/day L-citrulline, 500 mg/day Brazilian zala wood and 500 mg/day Brazilian cocoa (guarana)) for 1-4 weeks. All patients received multiple purgatives prior to commencement of COMB-4 treatment and, in the absence of purgatives, exhibited at least two or more of the following symptoms: incomplete feeling of excretion, score of 1-2 on Bristol stool, and stress during defecation. Data was collected on symptoms before and after treatment, including: bristol stool score, frequency of defecation, and sensation of excretion. Statistical analysis used the Wilcoxon rank-sum test.

Results

Bristol mean score increased from 1.5 to 3.3(p <0.01, fig. 1). The average number of stools per week increased from 3.3 to 8.4 after treatment (p <0.01, figure 1). Of the 10 patients, 8 were abdominal pain free (fig. 2), and 6/10 felt complete stool excretion after treatment (fig. 2). After commencement of COMB-4 treatment, 7/10 patients discontinued all other purgatives.

Conclusion

A mixture of ginger, L-citrulline, agaricus blazei murill, and guarana (COMB-4) can be a beneficial supplement to a treatment regimen for severe constipation.

Further tests on the efficacy of the present nutraceutical compositions in the treatment of constipation and other diseases of the gastrointestinal system are shown below.

Method

17 constipation patients were treated with COMB-4 (2-4 capsules per day, wherein each capsule consisted of 125mg ginger, 400mg L-citrulline, 125mg Quercus basjorana and 125mg cocoa Bacchard (guarana)) for 2-4 weeks. Constipation is defined as two or more of the following: incomplete sensation of excretion, bristol stool score 1-2 (hard, blocky nut-like or sausage-like BM), and stress during most bowel movements (Prichard, d.o., & bhaucha, A.E (2018), Recent advances in understating and marking chronic compliance.f1000research, 7,1640.doi: 10.12688/f1000research.15900.1). Patients were investigated before and after treatment for the approximate number of times they stood weekly, a typical bristol stool score, the presence of abdominal pain, and a feeling of incomplete excretion. Statistical analysis was performed using Wilcoxon rank sum test.

Results

After treatment with COMB-4, the mean stool frequency, bristol stool score and abdominal pain were all significantly improved weekly with p <0.0001 (figure 3). The average number of stools increased from 2.7 to 7.3 times per week (fig. 4). The patient reported an improvement in the sensation of complete stool excretion after receiving COMB-4 treatment (figure 5). The average bristol stool score increased from 1.5 points to 3.4 points, the stools were softer and more formed (fig. 6), and the patient had significantly reduced abdominal pain (fig. 7).

Conclusion

The combination of ginger, agaricus blazei, guarana and L-citrulline can improve defecation frequency and consistency and help alleviate constipation symptoms. The health care product can be a novel preparation for treating other serious constipation with poor conventional treatment effect.

While details of certain embodiments of the invention are described, they are provided as illustrative examples so that one of ordinary skill in the art can practice the invention. The details provided are not meant to limit the scope of the invention, but are provided as examples. If certain elements of the present invention can be partially or fully implemented using known components, only those portions of such known components that are necessary for an understanding and practice of the present invention will be described, and detailed descriptions of other components or formulation methods will be omitted so as to simplify the explanation of the present invention. Further, the present invention includes current and future known equivalents to the compositions and methods described herein. The invention is capable of other embodiments and of being practiced and carried out in various ways, and it will be appreciated by those skilled in the art that the conception upon which this invention is based may readily be utilized as a basis for the designing of other methods and compositions for carrying out the several purposes of the present invention.