WO2005110431A1 - Herbal product containing glucosamine - Google Patents

Abstract

Pharmaceutical compositions comprising a low dosage of glucosamine and at least one circulation-enhancing herbal product, such as Suberect Spatholobus Stem (aulis Spatholobi), Motherwort herb (Herba Leonuri), Tumeric Root Tuber (Radix Curcumae), Medicinal Cyathula Root (Radix Cyathulae), Sanchi (Radix Notoginseng), Danshen Root (Radix Salviae Miltorrhizae), Szechwan Lovage Rhizome (Rhizoma Chuanxiong), Yanhusuo (Rhizoma Corydalis), Zedoray Rhizome (Rhizoma Curcumae), Common Burreed Tuber (Rhizoma Sparganni), Peach Seed (Semen Persicae), Safflower (Flos Carthami), Gummi Olibanum, or Myrrha, are described. The aforementioned glucosamine and circulation-enhancing herbal compositions can be used to treat joint pain, arthritis, amenorrhea, dysmenorrhea, and muscle weakness.

Description

HERBAL PRODUCT CONTAINING GLUCOSAMINE PRIOR APPLICATION INFORMATION This application claims the benefit of US Provisional Application 60/572,120, filed May 19, 2004.

FIELD OF THE INVENTION The present invention relates generally to the field of pharmaceutical compositions. More specifically, the present invention relates to a pharmaceutical composition comprising glucosamine and one or more natural herbs.

BACKGROUND OF THE INVENTION Glucosamine is an amino sugar and is a major constituent of hyaluronic acid. In the body, the compound is taken up by chondrocytes and used in the synthesis of hyaluronic acid. By increasing the amount of hyaluronic acid, glucosamine supplementation leads to the rehydration of cartilage. Glucosamine supplementation also leads to an increase in proteoglycans in the extracellular matrix of articular cartilage, thereby increasing the overall amount and the structural integrity of the cartilage. Glucosamine is also used by chondrocytes to produce glycosaminoglycans, which lead to the production of proteoglycans that hold and hydrate connective tissue. With glucosamine supplementation, chondrocytes may be able to replenish the cartilage matrix and synovial fluid when cartilage is damaged. US Published Patent Application 20020064568 teaches a compound for arresting the inflammatory response in affected tissues comprising a palatability agent, an herbal phytochemical and a metabolic precursor. The herbal phytochemical may be selected from the group consisting of cayenne, ginger, tumeric, yucca, Devil's Claw, nettle leaf, Black Cohosh, alfalfa and celery seeds. When the metabolic precursor is glucosamine, the composition comprises 50-2000 mg of glucosamine per 25 pounds of body weight Anecdotal evidence indicates that over time, the effectiveness of glucosamine at a specific dosage diminishes and the dosage must be increased. However, it has been shown that higher dosages of glucosamine lead to polyuria and polydipsia and it has also been theorized that high glucosamine levels may increase insulin resistance, thereby increasing the risk of diabetes (2003, JAVMA 222: 431-432). Polyuria and polydipsia can lead to altered disposition of concurrently administered medications (prescription or over the counter) and electrolyte imbalance. Depending on the medication this can be harmful to patients. Moreover, glucosamine has been reported to cause CNS effects such as drowsiness, headache, somnolence, dermatological and cardiovascular effects (increased blood pressure) (2005, J. Complementary Integrative Medicine (2(1) article 1). Glucosamine's mechanism of action for these side effects is not known. However, most side effects are dose dependent, i.e., increase dose increase the probability of adverse reactions. The ability to decrease the dose yet maintain the main physiologic effect would be highly desirable. Clearly, a pharmaceutical composition is needed which comprises a lower initial dosage of glucosamine but has similar effectiveness compared to higher dosages so that the benefits can be enjoyed for a longer period of time.

SUMMARY OF THE INVENTION According to a first aspect of the invention, there is provided a pharmaceutical composition comprising glucosamine and at least one circulation- enhancing herbal product.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are now described. All publications mentioned hereunder are incorporated herein by reference. As used herein, "effective amount" refers to the administration of an amount of a given compound that achieves the desired effect, that is, the strengthening of cartilage and aiding in glycosaminoglycan synthesis. This provides its main benefit in osteoarthritis, enhanced mobility and decreased joint pain. Other physiological benefits of glucosamine include wound healing, psoriasis, inflammatory bowel disease and migraine prophylaxis. As used herein, the term "treating" in its various grammatical forms refers to preventing, curing, reversing, attenuating, alleviating, minimizing, suppressing or halting the deleterious effects of a disease state, disease progression, disease causitive agent other abnormal condition. Described herein is a pharmaceutical composition comprising glucosamine in combination with one or more herbal product that increases blood circulation. The herbal product may be selected from the group consisting of: Suberect Spatholobus Stem (aulis Spatholobi); Motherwort Herb (Herba Leonuri); Turmeric Root Tuber (Radix Curcumae); Medicinal Cyathula Root (Radix Cyathulae); Sanchi (Radix Notoginseng); Danshen Root (Radix Salviae Miltorrhizae); Szechwan Lovage Rhizome (Rhizoma Chuanxiong); Yanhusuo (Rhizoma Corydalis); Zedoray Rhizome (Rhizoma Curcumae); Common Burreed Tuber (Rhizoma Sparganii); Peach Seed (Semen Persicae), Safflower (Flos Carthami), Gummi Olibanum and Myrrha or combinations thereof. According to traditional Chinese herbal medicine these herbs are considered as "herbs that invigorate the blood" or "herbs that improve blood circulation and remove blood stasis" and therefore referred to herein as "circulation enhancing herbs" or "circulation enhancing herbal products". In the present case these herbs can be used alone or in combination with one or more other herbs, as discussed below. Some examples of these combinations include but are by no means limited to Peach Seed and Safflower, Suberect Spatholobus Stem and Turmeric Root Tuber, Zedoray Rhizome and Common Burreed Tuber, Gummi Olibanum and Myrrha, and Danshen Root and Szechwan Lovage Rhizome. As discussed below, the typical daily dosage of glucosamine on the market is approximately 43-257 mg per 25 lbs. However, as discussed herein, the addition of the herbal product improves blood circulation, meaning that a much lower amount of glucosamine can be used, for example, rather than the much higher dose of 43-257 mg/25 lbs, dosage can be reduced to 22-83 mg/ 25 lbs. As discussed above, the advantage of this arrangement is that the initial lower dosage is potentially less harmful and clearly less expensive. Furthermore, the dosage can be increased several times prior to reaching accepted threshold levels, as discussed above. Thus, in some embodiments, the pharmaceutical composition is in a tablet or capsule form which is arranged such that the dosage of glucosamine and circulation-improving herbal product in the tablet is approximately one-half of the dose that according to the instant invention is appropriate for an individual having an approximate weight of 175 pounds. That is, the dosage of a single tablet is such that an individual weighing 175 pounds would need to take 2 tablets. In these embodiments, the glucosamine may be at a dosage per tablet between 150-600 mg, as discussed above, and the herbal product or combination of herbal products may be at a dosage of 75-350 mg per tablet, as discussed below. As will be apparent to one of skill in the art, this is approximately 22-83 mg per 25 pounds per day. In one embodiment, the pharmaceutical composition comprises 300 mg glucosamine and 350 mg of an aqueous extract of Safflower (150 mg), common Flowering quince Fruit (150 mg), and Liquorice Root (50 mg). It is of note that in the traditional Chinese manner these three herbal products are combined. The Flowering quince fruit is useful for arthritis while the Liquorice Root is useful for those who are weak (lack of strength), or require pain relief (spasmodic pain in abdomen and limbs). In these embodiments, the dose would be 1-3 tablets daily (2 tablets for an average person of 175 lbs). Other examples of formulas include but are by no means limited to the following: Formula 1: glucosamine (100-400 mg), safflower (50-300 mg), peach seed

(20-50 mg), flowering quince fruit (50-300 mg), Liquorice Root (25-100 mg). Formula 2: glucosamine (100-400 mg), Suberect Spatholobus Stem (50-300 mg) and Turmeric Root Tuber (15-50 mg), flowering quince fruit (50-300 mg) and liquorice root (25-100 mg). Formula 3: glucosamine (100-400 mg), Zedoray Rhizome (30-50 mg), Common Burreed Tuber (20-50 mg), flowering quince fruit (50-300 mg), liquorice root (25-100 mg). Formula 4: glucosamine (100-400 mg), Gummi Olibanum (15-50 mg),

Myrrha (15-175 mg), flowering quince fruit (50-300 mg), liquorice root (25-100 mg). Formula 5: glucosamine (100-400 mg), Danshen Root (50-300 mg),

Szechwan Lovage Rhizome (10-30 mg), flowering quince fruit (50-300 mg), liquorice root (25-100 mg). Formula 6: glucosamine (100-400 mg), safflower (50-300 mg), flowering quince fruit (50-300 mg), liquorice root (25-100 mg), fructus mume (15-50 mg), herba ephedrae (15-50 mg). Formula 7: glucosamine (100-400 mg), safflower (50-300 mg), flowering quince fruit (50-300 mg), liquorice loot (25-100 mg), fructus mume (15-50 mg), ramulus cinnamomi cassiae (50-300 mg). In some embodiments, the aqueous extract is prepared by boiling the Safflower, common Flowering quince Fruit, and Liquorice Root in water for 1 hour. After the aqueous phase is decanted, more water is added and the material is boiled for an additional 30 minutes. The supernatant once again is decanted, additional water added and the material boiled for an additional 30 min. All aqueous phases are then combined and stored at 4°C overnight. The following day, the combined aqueous phases are centrifuged with the precipitate removed. Water is evaporated and the material concentrated and dried to powder form. Tablet filler and glucosamine are added and the tablet compressed or capsule formed. As will be appreciated by one of skill in the art, an effective amount of the above-described pharmaceutical composition may be used by an individual, for example, a mammal, to treat or ameliorate symptoms associated with one or more of the following: joint pain, arthritis, amenorrhea, dysmenorrhea and muscle weakness. The invention will now be described by way of examples. However, the invention is not limited to or limited by the examples.

EXAMPLE 1

Herbal Product Crude Product Extract Dosage (g) Dosage

(g) (mg)

Suberect Spatholobus Stem (aulis Spatholobi) 9-15 g 50-300

Motherwort Herb (Herba Leonuri) 9-30 g 50-600

Turmeric Root Tuber (Radix Curcumae) 3-9 g 15-50

Medicinal Cyathula Root (Radix Cyathulae) 4.5-9 g 20-50 Sanchi (Radix Notoginseng) 3-9 g 15-50

Danshen Root (Radix Salviae Miltorrhizae) 9-15 g 50-300

Szechwan Lovage Rhizome (Rhizoma Chuanxiong) 2-5 g 10-30

Yanhusuo (Rhizoma Corydalis) 3-9 g 15-50

Zedoray Rhizome (Rhizoma Curcumae) 6-9 g 30-50 Common Burreed Tuber (Rhizoma Sparganii) 4.5-9 g 20-50

Peach Seed (Semen Persicae) 4.5-9 g 20-50

Safflower (Flos Carthami) 9-15 g 50-300

Gummi Olibanum 3-9 g 15-50

Myrrha 3-12 g 15-175

As will be apparent to one of skill in the art, the doses indicated here represent the amount used in extraction of herbs. Other suitable amounts may be used and will of course depend on the nature and/or state of the herb used. An aqueous extract equivalent to the dosages shown in the Table above are extracted with a suitable solvent. The solvent is then evaporated and the remaining powder is reconstituted with tablet filler and glucosamine added, the powders are mixed appropriately and compressed to form the final tablet product. These concentrations can be used alone or in combination. Extraction methodology can use any volume that is reasonable for the manufacturing of the final product. Typically initial volumes used range 4-10 L.

EXAMPLE 2 We conducted an experiment whereby two groups of animals (rats) received either glucosamine alone or glucosamine and a herbal extract (the pharmaceutical composition comprises the equivalent of 300 mg glucosamine and 350 mg of an aqueous extract of Safflower (150 mg), common Flowering quince Fruit (150 mg), and Liquorice Root (50 mg)). Following 7 days of twice a day oral administration we took blood at 30, 45, and 60 minutes following oral administration on the last day of study. We analyzed the blood glucosamine concentration at these times and calculated the area under the concentration time curve (AUC). We found that glucosamine administered animals had 73.0 ug/ml/min while the glucosamine/herbal extract group had 114.9 ug/ml/min. Clearly the herbal group had almost twice as much glucosamine absorbed. While the preferred embodiments of the invention have been described above, it will be recognized and understood that various modifications may be made therein, and the appended claims are intended to cover all such modifications which may fall within the spirit and scope of the invention.

Claims

CLAIMS 1. A pharmaceutical composition comprising glucosamine and at least one circulation-enhancing herbal product. 2. The pharmaceutical composition according to claim 1 wherein the circulation-enhancing herbal product is selected from the group consisting of:

Suberect Spatholobus Stem (aulis Spatholobi); Motherwort Herb (Herba Leonuri); Turmeric Root Tuber (Radix Curcumae); Medicinal Cyathula Root (Radix Cyathulae); Sanchi (Radix Notoginseng); Danshen Root (Radix Salviae Miltorrhizae); Szechwan Lovage Rhizome (Rhizoma Chuanxiong); Yanhusuo (Rhizoma Corydalis); Zedoray Rhizome (Rhizoma Curcumae); Common Burreed Tuber (Rhizoma Sparganii); Peach Seed (Semen Persicae) Safflower (Flos Carthami), Gummi Olibanum and Myrrha. 3. The pharmaceutical composition according to claim 1 wherein the glucosamine is at a dosage of 100-500 mg. 4. The pharmaceutical composition according to claim 1 wherein the circulation-enhancing herbal product is at a dosage of 15-600 mg.