Blend of vip and VEGF growth factors for vaginal health

Abstract

A topical pharmaceutical blend for improving lubrication, moisturization, tissue regeneration, rejuvenation and blood flow of the vaginal area is provided. The pharmaceutical blends described herein may include vasoactive intestinal peptide (VIP) and vascular endothelial growth factor (VEGF). In some examples, the pharmaceutical blend may comprise both VIP and VEGF in less than about 1% by weight. The pharmaceutical blend can also include a lecithin carrier, and may be free of hormones.

Description

BLEND OF VIP AND VEGF GROWTH FACTORS FOR VAGINAL HEALTHCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 600,353, filed on November 17, 2023, titled “BLEND OF VIP AND VEGF GROWTH FACTORS FOR VAGINAL HEALTH”; which is herein incorporated by reference.FIELD OF THE INVENTION

[0002] The present disclosure relates to pharmaceutical compositions for treatment of vaginal atrophy. Specifically, the pharmaceutical compositions discussed herein include vasoactive intestinal peptide (VIP) and vascular endothelial growth factor (VEGF).BACKGROUND OF THE INVENTION

[0003] Atrophic vaginitis or vaginal atrophy occurs mostly in women after menopause when the body has less estrogen. Low estrogen levels can result in drying, thinning and inflammation of the vaginal walls. Vaginal atrophy can result in painful intercourse and also affects the urinary system. Sexual dysfunction in women and vaginal atrophy are normally treated with estrogen therapy. Estrogen therapies can increase mucous production, provide vasodilatory effects, and increase the general health of the vagina. Estrogen can be administered orally, topically, or by injection.SUMMARY OF THE INVENTION

[0004] Compositions and methods are provided for a pharmaceutical blend that is suitable for improving blood flow to the vaginal area. As discussed in more detail herein, the disclosed compositions and methods provide improvements for lubrication, moisturization, tissue regeneration, rejuvenation, and blood flow of the vaginal area.

[0005] In one example, this particular pharmaceutical blend may include vasoactive intestinal peptide (VIP) and vascular endothelial growth factor (VEGF). The pharmaceutical blend may comprise VIP and VEGF in an amount of less than about 1 wt. %, with from about 0.00001 wt. % to about 0.00002 wt. % being preferred. The disclosed pharmaceutical blend may contain a lecithin carrier.

[0006] In another example, this particular pharmaceutical blend may take the form of a topical formulation. This pharmaceutical blend may be administered topically in the form of creams, gels or patches. The topical pharmaceutical blend may be hormone free, such as an estrogen free blend.

[0007] In one example, this particular pharmaceutical blend may be used topically in the vaginal area for treatment of vaginal atrophy by increasing blood flow that enhances natural moisturization.

[0008] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.BRIEF DESCRIPTION OF THE DRAWING

[0009] Implementations of the present disclosure are described in detail below with reference to the attached drawing figures, wherein:

[0010] FIG. 1 depicts a graph illustrating phosphorylation of eNOS in VK2 / E6E7 cells induced after 15 minutes of treatment with a pharmaceutical blend;

[0011] FIG. 2A depicts a graph illustrating cyclin DI protein expression after 24 hours of a pharmaceutical blend treatment, including Western blot analysis showing cyclin DI and beta-actin protein levels;

[0012] FIG. 2B depicts a graph illustrating cyclin DI protein expression after 24 hours of a pharmaceutical blend treatment, including quantification of protein expression intensity normalized to beta-actin as internal control;

[0013] FIG. 3A depicts a graph illustrating migration of cultured human vaginal epithelium cells after 24 hours of treatment with a pharmaceutical blend, including cells stained with a fluorescent dye to visualize migration; and

[0014] FIG. 3B depicts a graph illustrating migration of cultured human vaginal epithelium cells after 24 hours of treatment with a pharmaceutical blend, including quantification of migration using a microplate reader.DETAILED DESCRIPTION OF THE INVENTION

[0015] Treatment of atrophic vaginitis or vaginal atrophy commonly involves estrogen therapy. Estrogen can be administered orally, topically or by injection to increase mucous production and provide vasodilatory effects. Estrogen therapy is a form of hormone replacement therapy (HRT) that often relieves symptoms such as irritation, dryness, itching and more, which can significantly increase the quality of life.

[0016] Additional treatments for atrophic vaginitis or vaginal atrophy include systemic HRT, non-hormonal moisturizers and lubricants, vaginal laser therapy, selective estrogen receptor modulators (SERMs), dehydroepiandrosterone (DHEA) treatment, platelet-rich plasma (PRP) therapy and vaginal pessaries.

[0017] Systemic HRT is normally used for treatment of menopausal symptoms, and it can also prevent bone loss and reduce fracture post-menopause. HRT involves the administration of female hormones, not limited to estrogen. Hormones such as progesterone can also be administered. Although HRT can be used for treatment of several conditions, HRT increases the levels of estrogen in the body, which can indirectly benefit vaginal tissue. DHEA is a hormone that has also been used to treat menopause symptoms and depression. DHEA can be converted into estrogen and testosterone in the body, helping improve the thickness and elasticity of the vaginal tissue when administered locally.

[0018] SERMs are hormone treatments normally used for osteoporosis or breast cancer that can manage how estrogen works in the body. SERMs drugs can mimic the effects of estrogen in certain parts of the body, such as the vagina, and therefore alleviate vaginal atrophy symptoms.

[0019] Additional treatments for vaginal atrophy can also include vaginal laser therapy. Vaginal laser therapy is a noninvasive treatment option for painful dryness and thinning of the vaginal walls. Vaginal laser therapy can restore vaginal tissue to premenopausal levels by stimulating the growth of new blood vessels which improves the production of elastin and collagen to restore vaginal walls.

[0020] Other treatments of vaginal atrophy can also include PRP therapy. This involves injecting a concentration of a patient's own platelets to promote healing and tissue regeneration.

[0021] Vaginal pessaries may sometimes be used and include devices inserted into the vagina to support the vaginal wall. While vaginal pessaries don't regenerate tissue, they can help in relieving some symptoms associated with vaginal atrophy.

[0022] However, for some patients, it might be desirable to have a hormone free treatment of vaginal atrophy or less invasive treatments for vaginal atrophy than those currently available, including some of those that have been described. Currently, non-hormonal treatment of vaginal atrophy is limited and may often be invasive. Other non-hormonal options may relieve some symptoms, such as moisturizers and lubricants that can provide temporary relief from vaginal dryness and discomfort during intercourse, but may not regenerate vaginal tissue as a treatment to vaginal atrophy.

[0023] Vasoactive intestinal peptide (VIP) is a neurotransmitter with vasodilatory properties. VIP plays a role in dilation of small vessels in the mesenteric blood supply. VIP exhibits a wide range of biological activities including the gastrointestinal tract, the endocrine and exocrine system, and smooth muscle. VIP may also be present in the genito-urinary system.

[0024] Vascular endothelial growth factor (VEGF) is a family of proteins that participate in angiogenesis, the formation of new blood vessels. Angiogenesis is a complex process that includes activation, migration and proliferation of endothelial cells for the formation of new blood vessels, and VEGF is involved in the entire sequence of events of angiogenesis. Certain vasculopathies, including coronary artery disease and limb claudication, rely on treatment with VEGF in either protein or gene form.

[0025] Lecithin is a group of chemicals that are part of phospholipids. Lecithin is used in the body for metabolic processes and to move fats. Phospholipids play important roles in the brain, blood, nerves, and tissues and are part of cell membranes. Lecithin can be used as carriers and stabilizers.

[0026] As used herein, “wt. %” means the percent concentration of the component in the formulation measured on a weight-to-weight basis. For example, 1 wt. % of component A=[(mass of component A) / (total mass of the pharmaceutical blend including the mass of component A)]xl00.

[0027] Reference to “about” a value or parameter herein refers to the usual error range for the respective value readily known to the skilled person in this technical field.

[0028] An example of the present disclosure may include a method for treating vaginal atrophy. The method may include providing a pharmaceutical blend comprising VIP and VEGF and applying the pharmaceutical blend to a vaginal tissue. The pharmaceutical blend may comprise VIP and VEGF in equal parts or different amounts. The pharmaceutical blend may comprise VIP and VEGF each in an amount less than about 1 wt. %.

[0029] In an aspect, the pharmaceutical blend comprises VIP in an amount of from about 0.000001 wt. % to about 1 wt. % and VEGF in an amount of from about 0.000001 wt. % to about 1 wt. %. In a preferable embodiment, the VIP and VEGF are each present in an amount from about 0.00001 wt. % to about 0.00002 wt. %.

[0030] In some aspects, VIP may be present in an amount of from about 0.1 wt. % to about 1 wt. %, or form about 0.01 wt. % to about 0.1 wt. %, or from about 0.0001 wt. % to about 0.001 wt. %, or from about 0.00001 wt. % to about 0.01 wt. %, or from about 0.000001 wt. % to about 0.0001 wt. %, or from about 0.00001 wt. % to about 0.0001 wt. %, or from about 0.000001 wt. % to about 0.00001 wt. %, or from about 0.00001 wt. % to about 0.00005 wt. %, or from about 0.00001 wt. % to about 0.00002 wt. %.

[0031] In some aspects, VEGF may be present in an amount of from about 0.1 wt. % to about 1 wt. %, or form about 0.01 wt. % to about 0.1 wt. %, or from about 0.0001 wt. % to about 0.001 wt. %, or from about 0.00001 wt. % to about 0.01 wt. %, or from about 0.000001 wt. % to about 0.0001 wt. %, or from about 0.00001 wt. % to about 0.0001 wt. %, or from about 0.000001 wt. % to about 0.00001 wt. %, or from about 0.00001 wt. % to about 0.00005 wt. %, or from about 0.00001 wt. % to about 0.00002 wt. %.

[0032] The pharmaceutical blend may be in the form of a topical formulation. The administration of the pharmaceutical blend as a topical formulation may be in the form of gels, creams, ointments, foams, sprays, powders, patches, balms, wipes, serums, lotions, and others.

[0033] An example of a method for treating vaginal atrophy may include providing a pharmaceutical blend comprising VIP and VEGF, and applying the pharmaceutical blend to a vaginal tissue. The VIP and VEGF may comprise any combination of concentrations previously described.

[0034] An example of a method for treating vaginal atrophy may include providing a pharmaceutical blend comprising VIP and VEGF, and applying the pharmaceutical blend to a vaginal tissue. The VIP and VEGF may comprise any combination of concentrations previously described. Based on application of the pharmaceutical blend, vaginal regeneration occurs. That is, an increase in vaginal tissue at the application site occurs as a results of application of the blend. In addition, an increase of lubrication of the vaginal tissue may occur after application of the pharmaceutical blend for treatment of vaginal atrophy. Based on application of the pharmaceutical blend, vaginal blood flow may be increased in the vaginal area.

[0035] Another example of a method for treating vaginal atrophy may include providing a pharmaceutical blend comprising VIP and VEGF, and applying the pharmaceutical blend to a vaginal tissue, where applying the pharmaceutical blend can include a single application or may be a series of applications, such as a monthly, weekly, daily, or multi-daily application scheduled. The VIP and VEGF may comprise any combination of concentrations previously described.

[0036] Any of the pharmaceutical blends previously described may include various carriers, including, but not limited to, a lecithin carrier.

[0037] Any of the pharmaceutical blends previously described may be hormone free. For instance, in aspects, the pharmaceutical blends do not comprise estrogen, progesterone dehydroepiandrosterone, or another like hormone.

[0038] In another example, any one of the pharmaceutical blends is suitable for improving lubrication, moisturization, tissue regeneration, rejuvenation, and blood flow of the vaginal area.

[0039] Another example of the present disclosure may include a method of manufacturing a hormone free pharmaceutical blend. The method may include combining VIP and VEGF to form a pharmaceutical blend. The pharmaceutical blend may comprise VIP and VEGF in equal parts or different amounts. The pharmaceutical blend may comprise VIP and VEGF each in an amount less than about 1 wt. %. The method can further comprise combining VIP and VEGF with a carrier, including, but not limited to a lecithin carrier. The method can further comprise combining additional active pharmaceutical ingredients or additives. The pharmaceutical blend can be applied to a vaginal tissue for treatment of vaginal atrophy, vaginal lubrication and vaginal moisturization.

[0040] The embodiments disclosed herein, including the pharmaceutical blend, and methods of using corresponding to the pharmaceutical blend, may be further understood by reference to the following non-limiting examples.EXAMPLES

[0041] Example 1 illustrated below is one example of a pharmaceutical blend that increases mucous production and provides vasodilatory effects. The table below includes components and an amount (wt. %) of each component.TABLE 1

[0042] Example 2 illustrated below describes the effects of the pharmaceutical blend on blood flow and cellular dynamics. A VK2 / E6E7 human vaginal epithelium cell line was used to study the effects of the pharmaceutical blend on eNOS phosphorylation, cyclin DI expression, and cell migration. The VK2 / E6E7 cell line was cultured in keratinocyte-serum free medium supplemented with 0.1 mg / ml human recombinant epidermal growth factor (EGF), 0.05 mg / ml bovine pituitary extract, and additional calcium chloride 44. 1 mg / L.

[0043] Using the VK2 / E6E7 cell line, Phospho-eNOS levels were measured using the Phospho-eNOS (SI 177) and Total eNOS ELISA Kit from Abeam. Activating endothelial nitric oxide synthase (eNOS) through phosphorylation has an effect on blood vessels. The activation leads to nitric oxide (NO) production, resulting in vasodilation and improved blood flow in the vaginal area. Since estrogen-induced eNOS phosphorylation and vasodilation typically occurs between 5 to 20 minutes after estrogen administration, phospho-eNOS levels were measured 15 minutes after treating cells with either estradiol (100 nM) or 0.5% of the pharmaceutical blend (resulting in a peptide concentration of 50 ng / ml). FIG. 1 compares phospho-eNOS levels after treatment with estradiol and the pharmaceutical blend. The pharmaceutical blend results in about 175% of phospho-eNOS levels compared to about 225% achieved using estradiol, and about 75% increase as compared to the control sample. The pharmaceutical blend significantly increased eNOS phosphorylation, suggesting potential vasodilatory effects as demonstrated in FIG. 1 .

[0044] Using the VK2 / E6E7 cell line, cyclin DI and beta-actin protein expression levels were analyzed by western blot, using antibodies from Cell Signaling Technology. Cyclin DI, a key cell-cycle regulator, is upregulated by estrogen treatment in postmenopausal vaginal epithelium, promoting the transition from the quiescent phase to proliferation phase. The VK2 / E6E7 cell line was treated with either estradiol (100 nM) or 0.5% of the pharmaceutical blend (resulting in a peptide concentration of 50 ng / ml). FIG. 2A shows western blot analysis showing cycling DI and beta-actin protein levels quantified in FIG. 2B, which provides a quantification of protein expression intensity normalized to beta-actin serving as the internal control. After 24 hours of treatment with the pharmaceutical blend, cyclin DI protein expression increased to about 7.0 compared to untreated cells at about 5.0 as demonstrated in FIG. 2B, indicating regulation of the cell cycle and maintenance of tissue integrity.

[0045] Using the VK2 / E6E7 cell line, cell migration was assessed by the Oris Cell Migration Assay Kit from Platypus Technologies. The VK2 / E6E7 cell line was treated with 0.03 % of the pharmaceutical blend resulting in a lower concentration of the peptide of around 3.3 ng / ml. FIG. 3A shows cells stained with a fluorescent dye to visualize migration. FIG. 3B shows quantification of cell migration using a microplate reader. Treatment with the pharmaceutical blend results in significant cell migration observed after 24 hours of about 150 % when compared to the estradiol treatment, that obtaining similar results as the control sample at around 100% cell migration. Cell cycle progression regulated cell migration, which is relevant in the healing of the vaginal lining, demonstrates that the pharmaceutical blend has the potential to improve wound healing.

[0046] The subject matter of the present technology is described with specificity herein to meet statutory requirements. However, the description itself is not intended to limit the scope of this disclosure. Rather, the inventors have contemplated that the claimed or disclosed subject matter might also be embodied in other ways, to include different steps or combinations of steps similar to the ones described in this document, in conjunction with other present or future technologies.

[0047] For purposes of this disclosure, the word “including," “having," and other like words and their derivatives have the same broad meaning as the word “comprising.” In addition, words such as “a” and “an,” unless otherwise indicated to the contrary, include the plural as well as the singular. Thus, for example, the constraint of “a feature” is satisfied where one or more features are present. Also, the term “or” includes the conjunctive, the disjunctive, and both a or b thus includes either a or b, as well as a and b).

[0048] Some example aspects of the invention that may be practiced from the forgoing disclosure include the following:

[0049] Aspect 1 : A method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization comprising: providing a pharmaceutical blend comprising less than about 1 wt. % vasoactive intestinal peptide (VIP) and less than about 1 wt. % vascular endothelial growth factor (VEGF); and applying the pharmaceutical blend to a vaginal tissue.

[0050] Aspect 2: Aspect 1 , wherein the pharmaceutical blend comprises from about 0.1 wt. % to about 1 wt. % VIP and from about 0.1 wt. % to about 1 wt. % VEGF.

[0051] Aspect 3: Aspect 1, wherein the pharmaceutical blend comprises from about 0.01 wt. % to about 0.1 wt. % VIP and from about 0.01 wt. % to about 0.1 wt. % VEGF.

[0052] Aspect 4: Aspect 1, wherein the pharmaceutical blend comprises from about 0.00001 wt. % to about 0.01 wt. % VIP and from about 0.00001 wt. % to about 0.01 wt. % VEGF.

[0053] Aspect 5: Aspect 1, wherein the pharmaceutical blend comprises from about 0.0001 wt. % to about 0.001 wt. % VIP and from about 0.0001 wt. % to about 0.001 wt. % VEGF.

[0054] Aspect 6: Aspect 1, wherein the pharmaceutical blend comprises from about 0.00001 wt. % to about 0.0001 wt. % VIP and from about 0.00001 wt. % to about 0.0001 wt. % VEGF.

[0055] Aspect 7: Aspect 1, wherein the pharmaceutical blend comprises from about 0.00001 wt. % to about 0.00002 wt. % VIP and from about 0.00001 wt. % to about 0.00002 wt. % VEGF.

[0056] Aspect 8: Aspect 1, wherein the pharmaceutical blend comprises from about 0.000001 wt. % to about 0.00001 wt. % VIP and from about 0.000001 wt. % to about 0.00001 wt. % VEGF.

[0057] Aspect 9: Any of Aspects 1-8, wherein the pharmaceutical blend is a topical formulation.

[0058] Aspect 10: Any of Aspects 1-9, wherein the pharmaceutical blend further comprises a lecithin carrier.

[0059] Aspect 11: Any of Aspects 1-10, wherein the pharmaceutical blend does not comprise estrogen.

[0060] Aspect 12: Any of Aspects 1-10, wherein the pharmaceutical blend does not comprise progesterone.

[0061] Aspect 13: Any of Aspects 1-10, wherein the pharmaceutical blend does not comprise dehydroepiandrosterone.

[0062] Aspect 14: Any of Aspects 1-13, wherein the pharmaceutical blend is hormone free.

[0063] Aspect 15: Any of Aspects 1-14, wherein the vaginal tissue is a vaginal tissue of a human patient.

[0064] Aspect 16: Any of Aspects 1-15, wherein the vaginal tissue regeneration occurs from application of the pharmaceutical blend.

[0065] Aspect 17: A pharmaceutical blend for treating vaginal atrophy, vaginal lubrication and vaginal moisturization comprising: less than about 1 wt. % vasoactive intestinal peptide (VIP) and less than about 1 wt. % vascular endothelial growth factor (VEGF).

[0066] Aspect 18: Aspect 17, further comprising from about 0.1 wt. % to about 1 wt.% VIP and from about 0.1 wt. % to about 1 wt. % VEGF.

[0067] Aspect 19: Aspect 18, further comprising from about 0.01 wt. % to about 0.1 wt. % VIP and from about 0.01 wt. % to about 0.1 wt. % VEGF.

[0068] Aspect 20: Aspect 19, further comprising from about 0.00001 wt. % to about 0.01 wt. % VIP and from about 0.00001 wt. % to about 0.01 wt. % VEGF.

[0069] Aspect 21: Aspect 20, further comprising from about 0.0001 wt. % to about 0.001 wt. % VIP and from about 0.0001 wt. % to about 0.001 wt. % VEGF.

[0070] Aspect 22: Aspect 21, further comprising from about 0.00001 wt. % to about 0.0001 wt. % VIP and from about 0.00001 wt. % to about 0.0001 wt. % VEGF.

[0071] Aspect 23: Aspect 22, further comprising from about 0.00001 wt. % to about 0.00002 wt. % VIP and from about 0.00001 wt. % to about 0.00002 wt. % VEGF.

[0072] Aspect 24: Aspect 23, further comprising about 0.000001 wt. % to about 0.00001 wt. % VIP and from about 0.000001 wt. % to about 0.00001 wt. % VEGF.

[0073] Aspect 25: Any of Aspects 17-24, wherein the pharmaceutical blend is a topical formulation.

[0074] Aspect 26: Any of Aspects 17-25, wherein the pharmaceutical blend further comprises a lecithin carrier.

[0075] Aspect 27: Any of Aspects 17-26, wherein the pharmaceutical blend does not comprise estrogen.

[0076] Aspect 28: Any of Aspects 17-27, wherein the pharmaceutical blend does not comprise progesterone.

[0077] Aspect 29: Any of Aspects 17-28, wherein the pharmaceutical blend does not comprise dehydroepiandrosterone.

[0078] Aspect 30: Any of Aspects 17-30, wherein the pharmaceutical blend is hormone free.

[0079] Aspect 31: A method of manufacturing a hormone free pharmaceutical blend comprising: combining less than about 1 wt. % vasoactive intestinal peptide (VIP) and less than about 1 wt. % vascular endothelial growth factor (VEGF).

[0080] Aspect 32: Aspect 31, wherein VIP is present in a concentration of from about 0.1 wt. % to about 1 wt. % and VEGF is present in a concentration of from about 0.1 wt. % to about 1 wt. %.

[0081] Aspect 33: Aspect 31, wherein VIP is present in a concentration of from about 0.01 wt. % to about 0.1 wt. % and VEGF is present in a concentration of from about 0.01 wt. % to about 0.1 wt. %.

[0082] Aspect 34: Aspect 31, wherein VIP is present in a concentration of from about 0.00001 wt. % to about 0.01 wt. % and VEGF is present in a concentration of from about 0.00001 wt. % to about 0.01 wt. %.

[0083] Aspect 35: Aspect 31, wherein VIP is present in a concentration of from about 0.0001 wt. % to about 0.001 wt. % and VEGF is present in a concentration of from about 0.0001 wt. % to about 0.001 wt. %.

[0084] Aspect 36: Aspect 31, wherein VIP is present in a concentration of from about 0.00001 wt. % to about 0.0001 wt. % and VEGF is present in a concentration of from about 0.00001 wt. % to about 0.0001 wt. %.

[0085] Aspect 37 : Aspect 31 , wherein VIP is present in a concentration of from about 0.00001 wt. % to about 0.00002 wt. % and VEGF is present in a concentration of from about 0.00001 wt. % to about 0.00002 wt. %.

[0086] Aspect 38: Aspect 31, wherein VIP is present in a concentration of from about 0.000001 wt. % to about 0.00001 wt. % and VEGF is present in a concentration of from about 0.000001 wt. % to about 0.00001 wt. % VEGF.

[0087] Aspect 39: Any of Aspects 31-38, wherein the hormone free pharmaceutical blend is a topical formulation.

[0088] Aspect 40: Any of Aspects 31-39, further comprising combining VIP and VEGF with a lecithin carrier.

[0089] Aspect 41: Any of Aspects 31-40, wherein the pharmaceutical blend does not comprise estrogen.

[0090] Aspect 42: Any of Aspects 31-40, wherein the pharmaceutical blend does not comprise progesterone.

[0091] Aspect 43: Any of Aspects 31-40, wherein the pharmaceutical blend does not comprise dehydroepiandrosterone.

Claims

CLAIMSWhat is claimed is:

1. A method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization, the method comprising: providing a pharmaceutical blend comprising: vasoactive intestinal peptide (VIP) that is less than about 1 wt. %; and vascular endothelial growth factor (VEGF) that is less than about 1 wt. %; and applying the pharmaceutical blend to vaginal tissue of a human patient, wherein vaginal tissue regeneration occurs from application of the pharmaceutical blend.

2. The method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization of claim 1, wherein the pharmaceutical blend further comprises: from about 0.000001 wt. % to about 1 wt. % VIP; and from about 0.000001 wt. % to about 1 wt. % VEGF.

3. The method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization of claim 1, wherein the pharmaceutical blend further comprises: from about 0.00002 wt. % to about 0.001 wt. % VIP; and from about 0.00002 wt. % to about 0.001 wt. % VEGF.

4. The method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization of claim 1, wherein the pharmaceutical blend further comprises: from about 0.00001 wt. % to about 0.00002 wt. % VIP; and from about 0.00001 wt. % to about 0.00002 wt. % VEGF.

5. The method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization of claim 1, wherein the pharmaceutical blend is a topical formulation.

6. The method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization of claim 5, wherein the pharmaceutical blend is topically applied as a cream, a gel, or a patch.

7. The method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization of claim 1, wherein the pharmaceutical blend further comprises a lecithin carrier.

8. The method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization of claim 1, wherein the pharmaceutical blend is hormone free.

9. The method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization of claim 8, wherein the pharmaceutical blend is free of estrogen.

10. The method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization of claim 8, wherein the pharmaceutical blend is free of progesterone.

11. The method of treating vaginal atrophy, vaginal lubrication and vaginal moisturization of claim 8, wherein the pharmaceutical blend is free of dehydroepiandrosterone.

12. A hormone free pharmaceutical blend for treating vaginal atrophy, vaginal lubrication and vaginal moisturization comprising: vasoactive intestinal peptide (VIP) that is less than about 1 wt. %; and vascular endothelial growth factor (VEGF) that is less than about 1 wt. %.

13. The hormone free pharmaceutical blend of claim 12, further comprising: from about 0.000001 wt. % to about 1 wt. % VIP; and from about 0.000001 wt. % to about 1 wt. % VEGF.

14. The hormone free pharmaceutical blend of claim 12, further comprising: from about 0.00002 wt. % to about 0.001 wt. % VIP; and from about 0.00002 wt. % to about 0.001 wt. % VEGF.

15. The hormone free pharmaceutical blend of claim 12, further comprising: from about 0.00001 wt. % to about 0.00002 wt. % VIP; and from about 0.00001 wt. % to about 0.00002 wt. % VEGF.

16. The hormone free pharmaceutical blend of claim 12, wherein the hormone free pharmaceutical blend is a topical formulation.

17. The hormone free pharmaceutical blend of claim 16, further comprising a lecithin carrier.

18. A method of manufacturing a hormone free pharmaceutical blend, the method comprising: combining vasoactive intestinal peptide (VIP) that is less than about 1 wt. % with vascular endothelial growth factor (VEGF) that is less than about 1 wt. %.

19. The method of manufacturing a hormone free pharmaceutical blend of claim 18, further comprising combining VIP and VEGF with a lecithin carrier.

20. The method of manufacturing a hormone free pharmaceutical blend of claim 18, wherein the VIP is from about 0.00001 wt. % to about 0.00002 wt. %; and the VEGF is from about 0.00001 wt. % to about 0.00002 wt. %.

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